tbuckley/cabot-search huggingface dataset:
CD133<sup>+</sup> cells in pulmonary arterial hypertension
Authors: Vasile Foris, Gabor Kovacs, Leigh M. Marsh, Zoltán Bálint, Martin Tötsch, Alexander Avian, Philipp Douschan, Bahil Ghanim, Walter Klepetko, Andrea Olschewski, Horst Olschewski
Journal: European Respiratory Journal (2016)

Circulating mononuclear cells may play an important role for the vascular remodelling in pulmonary arterial hypertension (PAH), but studies addressing multiple progenitor populations are rare and inconsistent. We used a comprehensive fluorescence-activated cell sorting analysis of circulating mononuclear cells in 20 PAH patients and 20 age- and sex-matched controls, and additionally analysed CD133 + cells in the lung tissue of five PAH transplant recipients and five healthy controls (donor lungs). PAH patients were characterised by increased numbers of circulating CD133 + cells and lymphopenia as compared with control. In PAH, CD133 + subpopulations positive for CD117 or CD45 were significantly increased, whereas CD133 + CD309 + , CD133 + CXCR2 + and CD133 + CD31 + cells were decreased. In CD133 + cells, SOX2, Nanog, Ki67 and CXCR4 were not detected, but Oct3/4 mRNA was present in both PAH and controls. In the lung tissue, CD133 + cells included three main populations: type 2 pneumocytes, monocytes and undifferentiated cells without significant differences between PAH and controls. In conclusion, circulating CD133 + progenitor cells are elevated in PAH and consist of phenotypically different subpopulations that may be up- or downregulated. This may explain the inconsistent results in the literature. CD133 + type 2 pneumocytes in the lung tissue are not associated with circulating CD133 + mononuclear cells.
IMPS-17BRANCHED-MULTIPEPTIDE IMMUNOTHERAPY FOR GLIOBLASTOMA USING HLA-A*0201-RESTRICTED CYTOTOXIC T-LYMPHOCYTE EPITOPE FROM BIRC5, CD99 AND ERBB2
Authors: Tae-Young Jung, Young-Hee Kim, Hyun-Ju Lee, Je-Jung Lee, Sook-In Jung
Journal: Neuro-Oncology (2015)

BACKGROUND: Branched-multipeptide has the increased molecular weight of the peptide which can elevate stable immunogenicity in the body. We identified and synthesized BIRC5, CD99 and ERBB2 peptides and their corresponding branched-multipeptide for HLA-A*0201 molecules. We investigated the possibility of immunotherapy for glioblastoma using cytotoxic T lymphocytes (CTLs) generated by branched-multipeptides pulsed dendritic cells (DCs). MATERIALS AND METHODS: We selected three peptides (BIRC5, CD99 and ERBB2), on the basis of their binding affinity, as determined by a peptide-T2 binding assay and their corresponding branched-multipeptide was synthesized using mini-polyethylene glycol (mini-PEGs) spacer. The function of DCs pulsed with multipeptide- cocktail was compared with DCs pulsed with branched-multipeptide by immunephenotype and cytokine secretion. We measured the functional activity for CTLs by using IFN-γ-enzyme linked immune absorbent spot (ELISPOT) assay. RESULTS: The stability of branched-multipeptide-T2 cells binding was relatively well maintained up to 24 hours compared to multipeptide cocktail. Based on FACS analysis which compared the phenotypes of multipeptide-cocktail and branched-multipeptide pulsed DCs, both DCs exhibited high expression of CD80, CD83 and CD86, which meant that both DCs resulted in efficient generation of DCs without altering the phenotype of the mature DCs. The both multipeptides pulsed DCs showed similarly increased IL-12p70, IL-12p40and IL-10 production. The CTLs that were stimulated by both multipeptides pulsed DCs displayed a greater number of IFN-γ-secreting cells against T2 cells loaded with both multipeptides and glioblastoma cell lines compared to those stimulated by un-pulsed DCs. CONCLUSION: Branched-multipeptide of BIRC5, CD99 and ERBB2 showed the stable binding with T cells and similar cytotoxic activity to target cells compared with multipeptide-cocktail. Branched-multipeptide can be the candidate of useful immunotherapeutic modalities for glioblastoma. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2014R1A1A1004469).
Aureomycin in the Treatment of Primary Atypical Pneumonia
Authors: Maxwell Finland, Harvey Shields Collins, Edward Buist Wells
Journal: New England Journal of Medicine (1949)

THE disease generally known as "primary atypical pneumonia" or "viral pneumonia" is now well established as a clinical entity. The fully developed case can usually be recognized by the nature and course of the symptoms, the character of the physical and roentgenographic findings in the lungs, the absence of sustained leukocytosis and the failure to find significant pathogenic bacteria in the blood, sputum or lungs or to obtain clinical cures with the available antibacterial agents. Confirmation of the diagnosis is obtained in a large proportion of cases by the demonstration of cold agglutinins in the patients' blood late in the . . .
Plethora of the Intracranial Venous Circulation in a Case of Polycythemia
Authors: Julius Loman, William Dameshek
Journal: New England Journal of Medicine (1945)

IN POLYCYTHEMIA vera, symptoms referable to the head greatly outrank in incidence those relating to any other bodily system.1 Actual cerebral vascular lesions are, furthermore, not infrequent. These include arterial or venous thromboses and hemorrhage, which is either intracerebral or subarachnoid in location. The development of extreme headache, amblyopia, papilledema and increased intracranial pressure in a case of well-marked secondary polycythemia led to studies that are of interest from the standpoint of intracranial dynamics, and to the conclusion that extreme plethora may result in changes indistinguishable from those occurring in other types of increased intracranial pressure.Case ReportA. F. . . .
Massive Gastrointestinal Bleeding Following Exposure to Low Pressure
Authors: W. Wilson Schier
Journal: New England Journal of Medicine (1947)

IN recent years reports of gastrointestinal hemorrhage from obscure and comparatively rare origins have been accumulating. Hematemesis is an exceedingly dramatic episode for the patient, and melena is equally so for the physician. After gastric or duodenal ulcer, varicosities of the esophagus and rectum or carcinoma of the stomach and large bowel have been dismissed, a diagnostic impasse is reached. This paper is the result of such a situation. No attempt is made to present an inclusive differential diagnostic study, but the possibilities of various lesions of more infrequent occurrence are considered. McBurney has been quoted as saying, "Deliver me . . .
Case 18-1996
Authors: Lisa H. Lerner, Elizabeth M. Bailey
Journal: New England Journal of Medicine (1996)

Presentation of CaseA newborn boy was admitted to the hospital because of a rash and respiratory distress.The infant was born at 3:35 p.m. by cesarean section at 34 weeks' gestation to a 37-year-old woman (gravida 3, para 2). The pregnancy had been complicated by gestational diabetes mellitus, which was controlled by diet, and by “bronchitis” during the two months before delivery; the mother was treated with amoxicillin. She also used an iron preparation and multivitamin tablets during the gestation. She reported that she had had varicella in childhood; did not use other medications, illicit drugs, alcohol, or tobacco; . . .
Bevacizumab in Renal-Cell Cancer
Authors: Guru Sonpavde
Journal: New England Journal of Medicine (2003)

To the Editor: In the report on their randomized, placebo-controlled, phase 2 trial evaluating bevacizumab, Yang et al. (July 31 issue)1 conclude that bevacizumab significantly prolongs the time to progression of metastatic renal-cell cancer. I believe this conclusion is inappropriate. Although the patients are randomly assigned to the treatment groups in a randomized phase 2 study, it is not equivalent to a phase 3 study. The purpose of a randomized phase 2 trial is to select one of several novel regimens for the next phase of testing. One can only be reassured that the selected regimen is probably not significantly . . .
Is oral ondansetron really efficacious in the control of cisplatin-induced delayed emesis?
Authors: M Martin
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.4.1401 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8648398 Is oral ondansetron really efficacious in the control of cisplatin-induced delayed emesis? M MartinxM MartinSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.4.1401 PDF "Is oral ondansetron really efficacious in the control of cisplatin-induced delayed emesis?." Journal of Clinical Oncology, 14(4), pp. 1401–1402© 1996 by American Society of Clinical Oncology
Studies on the Spread of the Right Atrial Activation by Means of Intracellular Microelectrode
Authors: Hiroshi Horibe
Journal: Circulation (1961)

Intracellular action potentials and the spread of the excitation in the right atrium were investigated on a whole specimen of a dog's or rabbit's right atrium by means of microelectorde method. The excitation was originated at a certain point of sinoatrial node and was transmitted very slowly in all directions in the node. The sinus excitation was transmitted rapidly through crista terminalis being transmitted to mm. pectinati. The atrial roof was activated by the stimuli coming from mm. pectinati. The thicker the muscle bundle, the faster the conduction and the longer the action potential duration. Conduction rate of the excitation through crista terminalis was about 1.5 meter per second and that in sinoatrial node was about 0.1 meter per second. The author could not observe any highly differentiated specific conduction system in the atrium like His' bundle or Purkinje fiber in the ventricles.
Abstract 563: Evaluation of EGFR mutation analysis performed by Sanger sequencing versus real-time PCR (EGFR RGQ PCR Kit)
Authors: Wolfgang Dietmaier, Irene Schardt, Petra Rümmele, Eva Geissinger, Arndt Hartmann, Robert Stöhr
Journal: Cancer Research (2015)

Abstract EGFR mutation analysis of exons 18, 19 and 21 is a standard analysis in routine molecular pathology for prediction of response of EGFR-tyrosine kinase inhibitors (EGFR-TKI) in non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the mutation detection using two widely used mutation analysis systems. For this purpose we analyzed exons 18, 19 and 21 of EGFR in 718 NSCLC with both nested PCR followed by direct Sanger sequencing and the EGFR RGQ PCR Kit (Qiagen). 694/718 samples were amplifiable and 676 samples allowed interpretable results by both methods. We found mutations in 74/676 (10,1%) samples by Sanger sequencing and in 91/676 (13,0%) using the RGQ Kit. There were 10/676 (1,5%) cases showing mutations only by Sanger Sequencing but not by the RGQ Kit. These mutations comprised four common EGFR-TKI sensitivity mutations in Exon21 (p.L858R (n = 2) and p.L861Q (n = 2)) as well as a complex deletion-insertion in exon 19 (n = 1). The other 5 mutations detected only by Sanger sequencing were uncommon and very rare mutations located in exon 18 and 21 which cannot be detected by the RGQ Kit due to its primer design. Vice versa, we found mutations in 21/676 samples using the RGQ Kit but not with Sanger sequencing. 20 of these mutations were common EGFR-TKI sensitivity mutations in exon 19 (deletions or complex delins, n = 15) and in exon 21 (p.L858R, n = 5) as well as a “p.G719X” mutation (n = 1) in exon 18. According to these data which includes mutations only in exons 18, 19 and 21 but not in exon 20 the mutation detection rate is higher using the RGQ-Kit than using the Sanger sequencing method (13,0% vs. 10,1%) especially in detecting common EGFR mutations associated with EGFR-TKI sensitivity. However the RGQ Kit fails in detecting uncommon and rare EGFR mutations for that this Kit is not designed and may produce non-informative results in some cases when ΔCT values are out of valid ranges whereas nested PCR followed by Sanger sequencing may still work. Citation Format: Wolfgang Dietmaier, Irene Schardt, Petra Rümmele, Eva Geissinger, Arndt Hartmann, Robert Stöhr. Evaluation of EGFR mutation analysis performed by Sanger sequencing versus real-time PCR (EGFR RGQ PCR Kit). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 563. doi:10.1158/1538-7445.AM2015-563
Rearrangement of the T-Cell Receptor β-Chain Gene in Non-T-Cell, Non-B-Cell Acute Lymphoblastic Leukemia of Childhood
Authors: Akio Tawa, Nobumichi Hozumi, Mark Minden, Tak W. Mak, Erwin W. Gelfand
Journal: New England Journal of Medicine (1985)

We studied 50 patients with childhood acute lymphoblastic leukemia (ALL), including 11 with T-cell ALL and 39 with non-T-cell, non-B-cell ALL. In addition to characterizing surface-antigen expression and immunoglobulin-gene rearrangement, we determined whether the T-cell receptor β-chain gene also undergoes somatic rearrangement. All 11 patients with T-cell ALL had rearrangements of the β-chain gene, with no persistence of the germline configuration. In two of these patients we demonstrated rearrangements of both the T-cell receptor gene and the immunoglobulin β-heavy-chain gene. All 39 patients with non-T-cell, non-B-cell ALL had immunoglobulin heavy-chain gene rearrangements; in addition, 10 had rearrangements of the T-cell receptor β-chain gene, indicating heterogeneity at the level of the T-cell receptor gene in this form of the disease. The results of our analysis of T-cell receptors and immunoglobulin heavy-chain genes offer new insight into normal and abnormal lymphocyte differentiation. (N Engl J Med 1985; 313: 1033–7.)
A Novel Method of Measuring Nasal Specific IgE in Systemic and Local Allergic Rhinitis Patients
Authors: Paloma Campo, Carmen Rondon, Ana Prieto del Prado, Maria Salas, Luisa Galindo, Ana Aranda, Cristobalina Mayorga, Arturo Ruiz, Gador Bogas, Leticia Herrero, Maria D. Cañamero, Miguel Blanca
Journal: Journal of Allergy and Clinical Immunology (2016)
PACE: A pivotal phase II trial of ponatinib in patients with CML and Ph+ALL resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation.
Authors: Jorge E. Cortes, Dong-Wook Kim, Javier Pinilla-Ibarz, Ronald Paquette, Philipp D. le Coutre, Charles Chuah, Franck E. Nicolini, Jane Apperley, Hanna Jean Khoury, Moshe Talpaz, John F DiPersio, Daniel J DeAngelo, Delphine Rea, Elisabetta Abruzzese, Martin C Müller, Michele Baccarani, Carlo Gambacorti-Passerini, Christopher D. Turner, Frank G. Haluska, Hagop Kantarjian
Journal: Journal of Clinical Oncology (2012)

6503 Background: Ponatinib is a potent, oral, pan-BCR-ABL inhibitor active against the native enzyme and all tested resistant mutants, including the uniformly resistant T315I mutation. Methods: The PACE (Ponatinib Ph+ALL and CML Evaluation) trial started Sept 2010. Pts with refractory CML (CP, AP or BP) or Ph+ALL resistant or intolerant (R/I) to dasatinib or nilotinib or with T315I received 45 mg ponatinib once daily. The trial is ongoing; enrollment completed Sept 2011. Data as of 17 Jan 2012 are reported. Results: 449 pts were enrolled, 5 of whom were ineligible (post-imatinib, non-T315I) but treated. Median age was 59 (18-94) yrs; 53% male. Diagnoses were: 271 CP-CML (R/I=207; T315I=64); 79 AP-CML (R/I=60; T315I=19); 94 BP/ALL (R/I=48; T315I=46). Median time from diagnosis to ponatinib was 6 yrs. Prior TKIs included imatinib (96%), dasatinib (85%), nilotinib (66%), bosutinib (7%); 94% failed ≥2 prior TKIs, 59% failed ≥3 prior TKIs. 83% had a history of resistance to dasatinib or nilotinib; 12% were purely intolerant. In CP, best response to most recent dasatinib or nilotinib was MCyR 25%. Frequent mutations confirmed at entry: 29% T315I, 8% F317L, 4% E255K, 4 % F359V, 3% G250E. Median follow-up was 6.6 months. Response rates are presented in the table. Overall, 64% remained on therapy (77% CP). Most frequent reasons for discontinuation were progression (12%) and AE (10%). Most common drug‑related AEs were thrombocytopenia (33%), rash (33%), dry skin (26%). Conclusions: Ponatinib has substantial activity in heavily pretreated pts and those with refractory T315I. Response rates continue to improve with longer follow-up. Multivariate analyses of predictors of outcome will be presented. [Table: see text]
OP0015 Ultrasound-Defined Tenosynovitis is a Strong Predictor of Early Rheumatoid Arthritis:
Authors: I. Sahbudin, L. Pickup, Z. Cader, A. Abishek, C.D. Buckley, G. Allen, P. Nightingale, P. de Pablo, K. Raza, A. Filer
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The EULAR Study Group for Risk Factors for Rheumatoid Arthritis (RA) recommends identification of new biomarkers for prediction of RA in early undifferentiated disease. The OMERACT Ultrasound Task Force recently established that US is a reproducible tool for evaluating tenosynovitis (TS) in RA<sup>1</sup>, which is a common manifestation of early RA. At present, the value of US-defined TS in the prediction of early RA is unknown. <h3>Objectives</h3> To explore the ability of US-defined TS to predict early RA compared with clinical and serological variables in an unselected very early arthritis cohort. <h3>Methods</h3> 107 patients with clinically apparent synovitis of at least one joint and symptom duration ≤3 months underwent clinical and multiple tendon US assessments and outcome was determined after 18 months by 1987 American College of Rheumatology criteria. A blinded US assessment determined the presence of grey scale and Power Doppler (PD) TS at 16 tendon regions: bilateral fingers (extensor and flexor compartments), wrists (extensor and flexor compartments), shoulders (biceps tendon), ankles (anterior extensors, peroneals, posterior tibialis) using a Siemens Acuson Antares scanner and 5–13 MHz linear array transducer. Grey scale and PD TS definition was based on the OMERACT Ultrasound Task Force recommendations<sup>1</sup> and recorded as binary outcomes. We compared the predictive values of US-defined TS with clinical and serological variables. <h3>Results</h3> 43 patients developed RA (VERA), 20 patients developed non-RA persistent disease (NRAP) and 44 patients had resolving disease at follow-up. A total of 1712 tendon regions in 107 patients were included in the analysis. All patient groups had evidence of tenosynovitis in one or more tendon compartments during baseline assessment (VERA 86%, NRAP 75%, resolving 70%). There were significant differences in the distribution of tendon involvement between the three groups including the Extensor Carpi Ulnaris tendon (ECU); [VERA 54%, NRAP 15%, resolving 18%; (p&lt;0.001)]. TS ultrasound variables were superior to clinical variables (early morning stiffness, symmetrical arthritis and hand joint arthritis) in the prediction of early RA. <h3>Conclusions</h3> This is the first study to show that US-defined TS is a strong predictor of early RA. Hand and ECU tendon scanning provides the optimal minimal ultrasound data to predict early RA. <h3>References</h3> Naredo E, D9Agostino MA, Wakefield RJ, et al. Reliability of a consensus-based ultrasound score for tenosynovitis in rheumatoid arthritis. Ann Rheum Dis 2013;72(8):1328-34. <h3>Disclosure of Interest</h3> None declared
Hyperacute rejection mimicry for cancer gene therapy
Authors: James Larkin, Colin D. Porter
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

4599 

This study aims to model hyperacute rejection (HAR) in a small animal as a potential therapeutic approach to cancer. Hyperacute rejection is a rapid immunological response mediated by the binding of natural antibodies and the consequent activation of the complement cascade leading to cell lysis. Solid organ xenotransplantation from pig to old World primate results in HAR due to recognition of the galactose(α1,3)galactose (αGal) epitope present on porcine endothelial cells by primate anti-αGal natural antibodies. The αGal epitope is synthesised by the enzyme (α1,3)galactosyl transferase ((α1,3)GT) that is absent in humans. The eventual therapeutic goal in humans of HAR mimicry would be to deliver the (α1,3)GT gene to tumour endothelial cells leading to vascular destruction. An (α1,3)GT ko mouse has been generated that, analogous with humans, does not express αGal on the cell surface and produces anti-αGal IgM. Serum titres of anti-αGal IgM can be increased by intraperitoneal immunisation with hypotonically lysed rabbit red blood cells. Murine complement is less potent than human complement and serum from immunised (α1,3)GT ko mice must be augmented with exogenous rabbit complement in order that in vitro cytotoxicity against αGal positive murine endothelial target cells is equivalent to that of human serum. The (α1,3)GT ko mouse has been crossed with a nude mouse to create a double knockout to allow the growth of xenografted human tumours. Subcutaneous co-injection of irradiated (α1,3)GT retrovirus producer cells with human tumour cells causes in vivo transduction with (α1,3)GT and consequent αGal cell surface expression. Pseudotyping of the retroviral envelope results in selective transduction of either the stromal or tumour cell compartment. In experiments in progress the intravenous administration of serum from immunised (α1,3)GT ko mice and rabbit complement is expected to cause lysis by HAR of αGal positive murine stromal cells in tumour bearing nude/ko animals. This is analogous with the hyperacute rejection of αGal positive hearts seen in immunised (α1,3)GT ko mice after the administration of rabbit complement in transplantation experiments. The effect of the destruction of a small number of stromal and vascular cells is expected to be amplified and cause the destruction of a larger number of tumour cells. This should be manifest as a reduction in the rate of tumour growth and in the histological disappearance of αGal positive areas in treated animals in comparison with untreated controls. The validity of hyperacute rejection mimicry as a therapeutic strategy for cancer is based on the assumption that individuals with cancer have adequate levels and function of anti-αGal antibodies and serum complement proteins. This is currently under investigation experimentally in a group of 50 individuals and data will be presented to address this question.
Cow's Milk (CM) Oral Immunotheray (OIT) Early Immunologic Shiftings
Authors: Jose Luiz M. Rios, Fabio C. Kuschnir, Alfredo Alves Neto, Flavia C. Loyola, Mary A. da Venda, Cristiane A. Iraha, Joao B.M. Rios
Journal: Journal of Allergy and Clinical Immunology (2016)
The Old Order Changeth, Yielding Place to New
Authors: Elliot L. Richardson
Journal: New England Journal of Medicine (1974)

DR. Colcock, members and guests of the Massachusetts Medical Society: It is a great honor for me and a personal pleasure as well to have the opportunity to deliver this lecture. Not only do I warmly recall prior occasions on which I've addressed this Society, but in one way or another my life has been drawn repeatedly back into the orbit of medicine. Born into a family of doctors, I thought I'd escaped by going to law school, but was then assigned to the Army Medical Department, because of a doctor's alertness in discovering that I'd memorized the eye chart. . . .