tbuckley/cabot-search huggingface dataset:
Topoisomerase IIa gene amplification predicts favorable outcome of tailored and dose-escalated anthracycline-based adjuvant chemotherapy in HER-2 positive breast cancer. Results from the randomized trial SBG 9401
Authors: M. M. Tanner, J. J. Isola, T. Wiklund, B. Erikstein, P. Kellokumpu-Lehtinen, P. Malmstrom, N. Wilking, J. Nilsson, J. Bergh
Journal: Journal of Clinical Oncology (2005)

9518 Background: Amplification of the HER-2/neu and topoisomerase IIα (TOP2A) genes has been linked to the effects of anthracyclines. Their role in predicting outcome of anthracycline-based adjuvant chemotherapy for breast cancer patients has remained controversial. Methods: High-risk breast cancer patients (with 5 or more positive axillary lymph nodes) were included in the present substudy of the SBG 9401 study, comparing an epirubicin-based regimen (9 courses of tailored and dose-escalated 5-fluorouracil, epirubicin and cyclophosphamide; FEC) with 3–4 courses of standard FEC followed by marrow-supported high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin (CTCb). Amplification of HER-2/neu and TOP2A were determined retrospectively on paraffin-embedded tumor tissue sections by chromogenic in situ hybridization (CISH), tissue samples were available from 396/525 (75%) patients. The primary end-point was time to recurrence of breast cancer. Results: HER-2/neu amplification, present in 32.7% of the tumors, was a strong prognostic factor for short relapse-free survival (p=0.0034), but did not predict treatment outcome in either treatment group separately. TOP2A gene amplification, present in 37% of HER-2/neu positive tumors, was associated with a statistically significantly better relapse-free survival than TOP2A non-amplified tumors in patients treated with tailored and dose-escalated FEC (HR=0.44, p=0.049). There was no such correlation seen in patients treated with standard FEC followed by the marrow-supported CTCb regimen (HR=0.95; p=0.87). TOP2A amplification was not associated with tumor size, lymph node status or hormone receptor status. Conclusions: Topoisomerase IIa gene amplification defines a subgroup of HER-2 amplified tumors patients who benefit from the tailored and dose-escalated FEC regimen, indicating that epirubicin should be given with sufficient dose intensity and total dose for a better outcome for this small subgroup. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Roche Finland Aventis, Bristol-Myers Squibb Hoffmann-La Roche Aventis, Lilly Oncology, Pierre Fabre, Roche
THE URINARY EXCRETION OF CREATINE IN ARTHRITIS
Authors: L W GRANIRER
Journal: Annals of Internal Medicine (1949)

Article1 May 1949THE URINARY EXCRETION OF CREATINE IN ARTHRITISLOUIS W. GRANIRERLOUIS W. GRANIRERSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-30-5-961 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe investigation here reported was undertaken to ascertain whether or not there was any abnormal excretion of creatine in rheumatoid and osteoarthritis. Within the last decade, creatine metabolism has been the object of very extensive research. The mechanism of the intermediate metabolism of creatine has not yet been elucidated completely. Evidence, however, exists to favor the view that glycine is converted to guanidinoacetic acid which is then methylated to form creatine.1 The first of these reactions probably takes place principally in the kidney and the transfer of free methyl groups occurs chiefly in the liver.Considerable material has been gathered...Bibliography1. BLOCHSCHOENHEIMER KR: Biological precursors of creatine, Jr. Biol. Chem., 1941, cxxxviii, 167-194. CrossrefGoogle Scholar2. KLEINER IS: Human biochemistry, 1945, C. V. Mosby & Co., St. Louis, p. 315. Google Scholar3. EVERETT MR: Medical biochemistry, 1942, P. B. Hoeber, New York, 413-430. Google Scholar4. MACLEOD JR: Physiology in modern medicine, C. V. Mosby & Co., St. Louis, p. 759. Google Scholar5. MAW GA: Creatine and creatinine excretion in women, Biochem. Jr., 1947, xli, 482-486. CrossrefGoogle Scholar6. TAYLORCHEW FHWB: Creatinuria in adult males, Am. Jr. Med. Sci., 1936, cxci, 257. Google Scholar7. TIERNEYPETERS NAJP: Mode of excretion of creatine and creatine metabolism in thyroid disease, Jr. Clin. Invest., 1943, xxii, 595. CrossrefGoogle Scholar8. WILKINSFLEISHMANN LW: Effects of thyroid on creatine metabolism, Jr. Clin. Invest., 1946, 360. CrossrefGoogle Scholar9. FOLIN O: The determination of creatinine and creatine in urine, Jr. Biol. Chem., 1914, xvii, 469-474. CrossrefGoogle Scholar10. BESTTAYLOR CHNB: The physiological base of medical practice, 1939, Wm. Wood & Co., Baltimore, p. 880. Google Scholar11. ALBANESEWANGERIN AADM: Creatine and creatinine excretion of normal adult males, Science, 1944, 59. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Broad Channel, New York*Received for publication June 8, 1948.The laboratory work was done at the New York Post-Graduate Medical School and Hospital. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byNiere und HarnUntersuchung der Körperflüssigkeiten und AusscheidungenCreatine Metabolism in Arthritis 1 May 1949Volume 30, Issue 5Page: 961-965KeywordsArthritisCreatineExcretionGlycineKidneysLiverOsteoarthritisResearch laboratories ePublished: 1 December 2008 Issue Published: 1 May 1949 PDF downloadLoading ...
Abstract 116: Relationship of Downtime and Cardiopulmonary Resuscitation Time to Neurologic Outcome in Patients with Nonshockable Rhythm Undergoing Therapeutic Hypothermia
Authors: Sanjeev U Nair, David Morris, Kamala Ramya Kallur, Alireza Hosseini-Khalili, Justin B Lundbye
Journal: Circulation (2011)

Background: Neurologic outcome in patients undergoing therapeutic hypothermia after resuscitation from cardiac arrest due to non-shockable rhythms is heterogeneous. We hypothesized that downtime an...
Abstract 20680: Human Endothelial Cells Derived from Induced Pluripotent Stem Cells Enhance Perfusion in a Murine Model of Peripheral Arterial Disease
Authors: Rufaihah A Jalil, Ngan F Huang, Sina Jame, Jerry Lee, Ha N Nguyen, Abhijit De, Sanjiv Ghambir, Renee Reijo-Pera, John P Cooke
Journal: Circulation (2010)

Stem cell therapy for angiogenesis and vascular regeneration has been investigated using diverse cell sources, including adult stem cells and embryonic stem cells. In the present study, we investigated the potential of endothelial cells (ECs) derived from human induced pluripotent stem cells (iPSCs) in promoting the perfusion of ischemic tissue in a murine model of peripheral arterial disease. The iPSCs were generated from human adult dermal fibroblasts using retrovirus-mediated transduction of Oct-4, Sox-2, Klf-4 and c-Myc. The iPSCs expressed pluripotency markers such as SSEA3/4 and alkaline phosphatase and formed teratomas in vivo. Endothelial lineage differentiation was initiated by culturing iPSCs for 14 days in differentiation media supplemented with BMP-4 and VEGF. CD144-positive iPSC-ECs were isolated using fluorescence activated cell sorting and were characterized by gene expression analysis, immunofluorescence staining and functional assays to confirm their endothelial identity. These purified i...
Reversal of asymmetry of the planum temporale in schizophrenia
Authors: R G Petty, P E Barta, G D Pearlson, I K McGilchrist, R W Lewis, A Y Tien, A Pulver, D D Vaughn, M F Casanova, R E Powers
Journal: American Journal of Psychiatry (1995)

The planum temporale is intimately involved in the generation and understanding of language and has been suggested to be a key area affected in schizophrenia. To explore temporal lobe abnormalities in schizophrenia, the authors measured the planum temporale, a normally asymmetric area lying on the superior part of the temporal lobe, in schizophrenic patients.High-resolution magnetic resonance imaging (MRI) scans were obtained for 14 right-handed schizophrenic patients and 14 healthy comparison subjects individually matched for age, sex, handedness, race, and parental socioeconomic status. The surface area of the planum temporale was measured by using MRI reconstruction techniques.There was striking reversal of the normal asymmetry (left larger than right) in planum temporale surface area in 13 of the schizophrenic patients but in only two of the comparison subjects. However, Heschl's gyrus (primary sensory cortex), which served as an anatomically contiguous nonheteromodal cortical comparison region, showed no difference between the left and right sides in either group. Severity of thought disorder in the patients was related to asymmetry.This is a clear demonstration of a reversal of expected symmetry in the brains of right-handed schizophrenic patients, which involves a region of key importance in normal human behavior. The nature of the abnormality strongly suggests that schizophrenia is a neurodevelopmental disorder.
Abstract 12863: Non-Cardiac Chest Pain: Is It Really?
Authors: Nicholas Boniface, Julian Kley, John Lisko, Brandon Mikolich, J Ronald Mikolich
Journal: Circulation (2014)

Background: Of patients with acute chest pain(CP), only 10% have acute coronary syndrome. About 20% of these CP patients have an obvious non-cardiac etiology, while the remaining 70% undergo diagnostic testing to exclude coronary atherosclerosis(CAD). Myocardial perfusion imaging(MPI) is commonly used to assess these patients. A normal MPI effectively excludes CAD and the patient is labeled as having “non-cardiac” CP. Late gadolinium enhancement(LGE) by Cardiac MRI(CMR) offers detection of pericardial disease. This study was undertaken to assess the role of CMR in CP patients with a normal MPI. Methods: An institutional cardiac imaging database was queried for all patients with new onset CP. The study was composed of those CP patients who did not have ACS or an obvious non-cardiac etiology. The cohort was divided into 2 groups. Group A patients underwent MPI as their initial test and were negative for ischemia, but had continued CP. Group B had CMR as their initial test and were negative for ischemia. The detection of pericarditis in these 2 patient groups was assessed using LGE of the pericardium. Results: 3,525 patients who presented with chest pain and no evidence of ACS underwent nuclear MPI. 347(9.8%) of these 3,525 patients had a normal nuclear MPI, but subsequently underwent a CMR for persistent chest pain and constituted Group A. 63 of 347(18.1%) Group A patients with a normal MPI had evidence of pericarditis on LGE. Group B had 505 patients with chest pain who underwent a CMR stress study, noting 461(82.4%) were normal, while 89(17.6%) had evidence of CAD. Of the 461 patients with a normal CMR stress, 80(19.2%) had evidence of pericarditis on LGE. Conclusions: About 10% of patients with CP and normal MPI may continue to complain of discomfort. These patients are usually labeled as “non-cardiac”, and often undergo gastrointestinal and musculoskeletal evaluation. Evaluation of this group of patients with CMR shows that 18-19% have pericarditis by LGE and are incorrectly labeled as “non-cardiac”. Newer treatments for pericarditis with colchicine/non-steroid anti-inflammatory drugs have high success rates, while undiagnosed/untreated pericarditis is likely a precursor to constrictive disease, making the need for a correct initial diagnosis imperative.
A candidate gene for human neurodegenerative disorders: a rat PKCγ mutation causes a Parkinsonian syndrome
Authors: Nicola J. Craig, María B. Durán Alonso, Kim L. Hawker, Paul Shiels, Thora A. Glencorse, Jacqueline M. Campbell, Neil K. Bennett, Maurice Canham, Denise Donald, Mary Gardiner, Desmond P. Gilmore, Raymond J. MacDonald, Kirsty Maitland, Andrew S. McCallion, David Russell, Anthony P. Payne, Roger G. Sutcliffe, R. Wayne Davies
Journal: Nature Neuroscience (2001)
Abstract 5432: Mutation of Three Amino Acids in the Disulfide-Ring of a CNP Based Chimeric Natriuretic Peptide Alters its Vascular Properties
Authors: Horng H Chen, Brenda K Huntley, Candace Y Lee, Fernando L Martin, John A Schirger, John C Burnett
Journal: Circulation (2008)

BACKGROUND: C-type natriuretic peptide (CNP) is a 22-amino-acid peptide produced mainly in the endothelium with potent cardiac unloading and modest blood pressure lowering actions, but minimal renal actions. Based on our previous knowledge, we recently fused a 6 aa sequence from BNP to the C-terminus and a 5 aa sequence from ANP to the N-terminus of CNP. This novel hybrid peptide, CBA-NP, has cardiac unloading actions and mild hypotensive effects similar to CNP. Importantly however, the N and C terminus alterations resulted in potent renal excretory actions. here we test the hypothesis that the 3 aa GSM 15–17 in the disulfide-ring mediate the vascular and hypotensive actions. We therefore mutated GSM 15–17 to REA 15–17 , which we named ABC-NP and compared its in vivo and in vitro actions to CBA-NP. METHODS: We determined the cardiorenal and humoral actions of intravenous bolus administration of CBA-NP (n=5) and ABC-NP (n=5) at 25 microgram/Kg in 2 separate group of normal anesthetized dogs. We also assessed the cGMP response of both peptides in human aortic endothelial cells (HAEC), human cardiac fibroblast (HCF) and isolated canine glomeruli. * p&lt;0.05 RESULTS: IV bolus administration of CBA-NP and ABC-NP resulted in diuresis* and natriuresis*. There was a significant decrease in mean arterial blood (MAP) pressure with CBA-NP (126±6 to113±7 mmHg*) but no change with ABC-NP(126±8 to126±8 mmHg) . In addition, the reduction in pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP) was significantly greater with CBA-NP as compared to ABC-NP. cGMP generation in HAEC and HCF was minimal with ABC-NP and was significantly higher with CBA-NP*. In contrast, cGMP generation was similar in isolated glomeruli between the two peptides. CONCLUSION: Our studies demonstrates that mutation of three amino acid (aa) residues within the CNP ring of CBA-NP from GSM 15–17 to REA alters the vascular but not the renal excretory properties. Hence by this strategic mutation within the ring of CBA-NP, we have designed a renal specific peptide ABC-NP resulting in new sequence specific functional information which can be used to design organ specific therapeutic peptides with unique properties tailored for a specific disease state.
A persistent problem with scabies in and outside a nursing home in Amsterdam: indications for resistance to lindane and ivermectin
Authors: J A van den Hoek, J A van de Weerd, T D Baayen, P M Molenaar, G J Sonder, I M van Ouwerkerk, H JC de Vries
Journal: Eurosurveillance (2008)

An ongoing outbreak of scabies in and outside a nursing home in Amsterdam is described. Despite standard treatment with lindane and ivermectin, many recurrences were observed which suggested resistance to these drugs. After treatment with 5% permethrine, the patients were finally cured.
Syphilis of the Stomach—A Study of Eight Cases
Authors: John B. Fitts
Journal: Annals of Internal Medicine (1930)

Article1 December 1930Syphilis of the Stomach—A Study of Eight CasesJOHN B. FITTS, M.D., F.A.C.P.JOHN B. FITTS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-4-6-628 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptVisceral syphilis has become of increasing interest and importance in recent years due to more accurate diagnosis, and to an appreciation of its wider incidence.Lesions of tertiary syphilis manifesting themselves in the cardio-vascular and central nervous systems are being more and more emphasized today. The gastro-intestinal tract is less often affected, perhaps, by the spirocheta pallida than any of the viscera. Gastric symptoms in syphilitics may be many and varied, they may be independent and superimposed upon an existing syphilis, or the expression of symptoms of central nervous system lues, as gastric crises, or reflexly from syphilis of other... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Atlanta, Ga.*From the Department of Medicine, School of Medicine, Emory University. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byLEGENDS TO FIGURES ON ILLUSTRATIVE PLATEDie Krankheiten des MagensSyphilis of the stomach with special reference to errors in diagnosis 1 December 1930Volume 4, Issue 6Page: 628-631KeywordsCentral nervous systemGastroenterology and hepatologyLesionsSyphilis ePublished: 1 December 2008 Issue Published: 1 December 1930 PDF downloadLoading ...
Multi-analyte profiling of inflammatory markers in COPD sputum
Authors: Frauke Pedersen, Gereon Lauer, Gianluca Quintini, Olaf Holz, Anne-Marie Kirsten, Helgo Magnussen, Klaus F. Rabe, Torsten Goldmann, Henrik Watz
Journal: European Respiratory Journal (2014)

New technology approaches allow to measure multiple protein analytes in inflammatory conditions like COPD. Here we evaluated, whether it is feasible to apply the Myriad RBM Human Inflammation Multi Analyte Profiling (MAP ® , Rules Based Medicine, Austin, TX) platform to sputum supernatant of patients with COPD and evaluated the effects of sputum processing with dithiotreitol (DTT) on the number and concentration of inflammatory markers.  Induced sputum samples of 20 patients with stable COPD (mean FEV 1 , 60.2% pred.) were processed in parallel with and without DTT and the respective supernatants were analysed using the MAP panel.  31 inflammatory proteins out of 46 analytes present in the panel could be measured in sputum sampels processed with DTT. 18 proteins could be measured in sputum samples processed without DTT. Concentrations of VDBP, α-2-Macroglobulin, Haptoglobin, AAT, VCAM-1 and Fibrinogen were significantly higher in samples processed with DTT. In contrast, concentrations of Ferritin, TIMP-1, MCP-1, MIP-1β, ICAM-1, and Complement C3 were significantly lower in sputum samples processed with DTT. The concentrations of the 12 proteins that could be detected both after processing with or without DTT were significantly correlated (all Pearson correlation coefficients g0.65). The concentrations of IL-6, IL-8, MMP-3, β-2-microglobulin, VEGF, and TNFR2 were similar in sputum samples processed with or without DTT.  Two thirds of the inflammatory proteins present in the Human Inflammation MAP ®  panel could be measured in COPD sputum supernatant following standard processing with DTT.
Skeletal myogenic potential of human and mouse neural stem cells
Authors: Rossella Galli, Ugo Borello, Angela Gritti, M. Giulia Minasi, Christopher Bjornson, Marcello Coletta, Marina Mora, M. Gabriella Cusella De Angelis, Roberta Fiocco, Giulio Cossu, Angelo L. Vescovi
Journal: Nature Neuroscience (2000)
STUDIES IN THE CELLULAR EXUDATES OF BOWEL DISCHARGES. III. THE DIAGNOSTIC SIGNIFICANCE OF CELLULAR EXUDATE STUDIES IN CHRONIC BOWEL DISORDERS
Authors: Z. Bercovitz
Journal: Annals of Internal Medicine (1941)

Article1 February 1941STUDIES IN THE CELLULAR EXUDATES OF BOWEL DISCHARGES. III. THE DIAGNOSTIC SIGNIFICANCE OF CELLULAR EXUDATE STUDIES IN CHRONIC BOWEL DISORDERSZ. BERCOVITZ, M.D., F.A.C.P.Z. BERCOVITZ, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-14-8-1323 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe purpose of this paper is to give the practical applications of the findings of a series of studies of the cellular exudates of bowel discharges.The microscopic examination of bowel discharges for the presence or absence of cells affords the general practitioner a very simple, yet most effective method of determining whether or not there are pathological changes in the bowel wall. The presence of cells in the bowel discharges indicates that pathological changes are taking place. This knowledge is of particular value when following the progress of an inflammatory lesion. The decrease of cells found in the bowel...Bibliography1. BERCOVITZ Z: The new sigmoid cannula, Am. Jr. Digest. Dis. and Nutr., 1936, iii, 499-500. CrossrefGoogle Scholar2. BERCOVITZ Z: Studies in cellular exudates of bowel discharges. I. Control observations in 1123 patients, 7 autopsies and 3 dog specimens, Jr. Lab. and Clin. Med., 1940, xxv, 788-795. Google Scholar3. BERCOVITZFULLER ZCC, to be published. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Presented before the symposium on Ulcerative Colitis held at the New York Post-Graduate Medical School and Hospital, September 25, 1938. Received for publication October 27, 1939.Assistant Clinical Professor of Medicine, New York Post-Graduate Medical School of Columbia University; Assistant Attending Physician, Second Medical (Cornell) Division, Bellevue Hospital, New York. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDifferential clinical features and stool findings in shigellosis and amoebic dysenteryCytologic diagnosis of malignancies of the lower bowel and rectumFever in carcinoma of the colon and rectumGastrointestinal AllergyDiseases of anorectum and colon review of certain recent contributions 1 February 1941Volume 14, Issue 8Page: 1323-1340KeywordsCellsHospital medicineLesionsUlcerative colitis ePublished: 1 December 2008 Issue Published: 1 February 1941 PDF downloadLoading ...
Abnormal Cardiac High Energy Phosphate Metabolism and Impaired Diastolic Function after Mt Everest: A Reversible Model of Early Heart Failure?
Authors: Cameron J Holloway, Andrew J Murray, Lowri Cochlin, Yaso Emmanuel, Denny H Levett, Oliver J Rider, Damian J Tyler, Matthew Robson, Jane M Francis, Nicholas S Knight, Stefan Neubauer, Hugh E Montgomery, Michael P Grocott, Kieran Clarke
Journal: Circulation (2008)