tbuckley/cabot-search huggingface dataset:
228. AAV Mediated Hypoxia-Inducible VEGF Expression and Neovascular Formation in Ischemic Pig Myocardium
Authors: Hua Su, Yerem Yeghiazarians, Andrew Lee, Yu Huang, Janice Arakawa-Hoyt, Jianqin Ye, Gina Orcino, William Growssman, Yuet W. Kan
Journal: Molecular Therapy (2006)

Rapid, efficient overexpression of angiogenic growth factors in the peri-infarct zone is a promising approach for gene therapy of acute myocardium infarction. Patients suffering from an acute myocardial infarction often require invasive treatment, and gene transfer could be performed in combination with intravascular revascularization strategies or with bypass surgery. Many angiogenic factors such as vascular endothelial growth factor (VEGF), angiopoietins, fibroblast growth factor-4 (FGF-4) and placental growth factor (PlGF) have been shown to be potent inducers of arteriogenesis. VEGF is the most potent among these factors as it is capable of increasing proliferation and migration of endothelial and vascular smooth muscle cells, and attracting stem cell homing. In our previous studies, we have induced neovascular formation in ischemic mouse hearts with adeno-associated viral vector (AAV) mediated VEGF gene transfer. To avoid the harmful effect of excessive angiogenesis, we have constructed an AAV vector (MLCVEGF) with 9 copies of the hypoxia-response element (HRE) of the human erythropoietin (EPO) gene and the promoter of the rat myosin light chain 2v (MLC-2v) controlling VEGF gene expression. Since information derived from mouse model may not be directly applicable to human and the pig heart closely resembles the human heart closely, we tested the hypotheses that MLCVEGF can also mediate hypoxia- inducible VEGF expression and induce neovascular formation in the pig heart. We injected 1×1011 genomes of MLCVEGF or CMVVEGF (AAV vector with CMV promoter driving VEGF expression) into normal and ischemic pig myocardium after 90 minutes of occlusion and reperfusion of the left anterior descending coronary artery (LAD). CMVLacZ vector (AAV vector with CMV promoter driving LacZ gene expression) was used as control. All vectors were packaged in AAV serotype 1 capsid. Myocardiums were collected 2 weeks after the vector injection. Gene expression was analyzed by real-time RT-PCR and immunohistochemical staining. Capillaries and a-actin positive vessels were quantitated on anti PECAM-1 and smooth muscle a-actin antibody stained sections. We observed robust LacZ and VEGF gene expression at CMVLacZ and CMVVEGF injection sites and found more capillaries and a-actin positive vessels at VEGF vector injected sites than CMVLacZ injection sites. VEGF expression mediated by MLCVEGF vector was low in normal myocardium and was induced about 40-fold in ischemic myocardium 2 weeks after myocardial infarction and vector injection. Conclusions: 1) AAV serotype 1 can infect pig myocardium efficiently. 2) AAV vector containing VEGF controlled by MLC-2v promoter and 9 copies of EPO HRE can mediate hypoxia-inducible gene expression and induce neovascular formation in the pig myocardium.
Airways obstruction associated with graft versus host disease after bone marrow transplantation.
Authors: S E Wyatt, P Nunn, J M Hows, J Yin, M C Hayes, D Catovsky, E C Gordon-Smith, J M Hughes, J M Goldman, D Galton
Journal: Thorax (1984)

Eight patients, five with chronic granulocytic leukaemia and three with severe aplastic anaemia, developed moderately severe airflow obstruction after allogeneic bone marrow transplantation. All eight had clinically and radiologically normal lungs before undergoing transplantation. Treatment in the patients with chronic granulocytic leukaemia before transplantation included high dose total body irradiation. All eight patients developed acute and chronic graft versus host disease after transplantation. The pulmonary syndrome consisted of cough, dyspnoea, and wheezing beginning six to 20 weeks after transplantation, with ratios of forced expiratory volume in one second (FEV1) to vital capacity (VC) falling to 60% or less of predicted values. The three patients with severe aplastic anaemia had relatively mild graft versus host disease and acute chest infection may have initiated or contributed to their airways obstruction, which subsequently resolved. The five patients with chronic granulocytic leukaemia had more severe graft versus host disease and more progressive respiratory problems; two died and three continued to have persistent airflow obstruction 11, 15, and 20 months after transplantation. None of those with chronic granulocytic leukaemia improved. Transfer factor (TLCO) was reduced in all patients after bone marrow transfer and did not improve; in the patients with chronic granulocytic leukaemia the reduction in TLCO preceded the fall in FEV1/VC ratio. Open lung biopsy in one of the patients with chronic granulocytic leukaemia showed obliterative bronchiolitis with lymphocytic infiltration consistent with graft versus host disease. Bronchodilators were of no benefit in the management of these patients, but prompt treatment of infection and early use of corticosteroids may have contributed to the improvement seen in the patients with severe aplastic anaemia.
414 IMMUNOHISTOCHEMISTRY FOR AGRIN AND CD34 IN THE DISCRIMINATION OF BENIGN VERSUS MALIGNANT LESIONS OF THE LIVER PARENCHYMA
Authors: P. Tatrai, A. Somoracz, E. Batmunkh, A. Kiss, P. Schirmacher, P. Nagy, Z.S. Schaff, I. Kovalszky
Journal: Journal of Hepatology (2008)
Discussion: Clinical features, epidemiology, classification criteria, and quality of life in psoriasis and psoriatic arthritis
Authors: D D Gladman
Journal: Annals of the Rheumatic Diseases (2005)

Single-Cell mRNA sequencing has enhanced our knowledge of the cell populations found in individual tissues or disease states. However, low correlation between mRNA and protein expression levels hinders our understanding of biology and disease. Traditional single cell protein assays are limited in the number of parameters that can be achieved within one experiment. Here we use oligo-conjugated antibodies (Ab-seq) in combination with massively parallel single cell mRNA sequencing on the BD Rhapsody™ platform to simultaneously measure the protein and mRNA content of individual human blood cells (PBMCs). To accomplish this, a 30+ parameter Ab-seq panel against immune relevant cell surface markers was paired with the BD Rhapsody™ Immune Response panel (a targeted gene expression panel consisting of 399 targets). The Multi-omics data from this single workflow experiment provides a measurement of both gene expression and protein expression. The digital measurements are rendered free of PCR bias through the use of the unique molecular indices (UMIs). Our results show that protein expression detected with Ab-seq is highly sensitive and specific. Protein expression patterns correlate well with results from flow cytometry data on the same samples. Ab-seq allowed the robust detection of expressed genes even when their cognate mRNA transcripts have low abundance. Certain markers cannot be easily distinguished at the mRNA level (i.e. isoforms CD45RA and CD45RO) but are easily distinguished at the protein level. Our study shows successful analysis of protein and mRNA expression data within a single workflow, and should enable the further elucidation single cells within different tissues, developmental time points, and disease states.
TCT-867 Clinical Impact of Persistent Left Bundle Branch Block After CoreValve Revalving System Implantation. Insight from a Multicenter Italian Registry
Authors: Luca Testa, Mauro Agnifili, Francesco Bedogni, N. Edy Brambilla, Antonio Colombo, Federico De Marco, Stefano De Servi, Federica Ettori, Silvio Klugmann, Stefania Lanotte, Roberto Latini, Maria Luisa Laudisa, Massimo Napodano, Anna Sonia Petronio, Samuele Pizzocri, Arnaldo Poli, Angelo Ramondo, Corrado Tamburino
Journal: Journal of the American College of Cardiology (2012)
A mistake that might have been my last
Authors: D. Landsborough
Journal: BMJ (2003)

In the years 1943, 1944, and 1945 there occurred late spring sub-epidemics of bubonic plague in the city of Chuanchow, in Fujian province in south China. Hospital admissions were between 88 and 69 each year.

I was called to see a patient in the emergency room of the hospital. She was a young woman, semi-comatose with a high …
Direct Serum Assay for Cell-Free <i>Bmi-1</i> mRNA and Its Potential Diagnostic and Prognostic Value for Colorectal Cancer
Authors: Xin Zhang, Xiaoyun Yang, Yanli Zhang, Xinfeng Liu, Guixi Zheng, Yongmei Yang, Lili Wang, Lutao Du, Chuanxin Wang
Journal: Clinical Cancer Research (2014)

Cell-free Bmi-1 mRNA is stably detectable in the serum/plasma and is associated with the development and progression of some tumors. Previous methods detecting extracellular Bmi-1 mRNA with RNA extraction are inefficient. This study developed a novel reverse transcription quantitative PCR (RT-qPCR) approach directly applied in serum (RT-qPCR-D) to quantify Bmi-1 mRNA, and assessed its diagnostic and prognostic potential in colorectal cancer.The feasibility of the RT-qPCR-D method was first analyzed in 50 serum samples. Then, using the RT-qPCR-D method, Bmi-1 mRNA expression was validated in serum from an independent cohort of patients with 87 normal colonoscopy, 76 hyperplastic polyp, 82 inflammatory bowel disease, 68 adenoma, and 158 colorectal cancer. Receiver operating characteristic (ROC) curves and Cox analyses were used to evaluate its diagnosis and prognosis value, respectively.In a pilot study, levels of Bmi-1 mRNA were increased in colorectal cancer serum samples detected by RT-qPCR-D and significantly associated with results obtained by RT-qPCR. In a validation cohort, serum Bmi-1 mRNA levels were significantly elevated in the colorectal cancer group and the adenoma group when compared with other groups. The area under ROC curve distinguishing colorectal cancer from benign colorectal diseases was 0.888, with 72.2% sensitivity and 94.9% specificity, which was superior to carcinoembryogenic antigen. Bmi-1 mRNA levels were significantly associated with survival. Cox analysis indicated Bmi-1 mRNA was an independent prognostic factor for overall survival.Detection of cell-free Bmi-1 mRNA in serum by RT-qPCR-D is a simple and noninvasive approach and may be used for colorectal cancer diagnosis and prognosis.
Age, Renal Tubular Phosphate Reabsorption, and Serum Phosphate Levels in Adults
Authors: Massimo Cirillo, Carolina Ciacci, Natale G. De Santo
Journal: New England Journal of Medicine (2008)

To the Editor: A relation between age and serum phosphate levels in adults has been recognized since 1969.1 We used data from the Gubbio Population Study to analyze serum phosphate levels and renal...
1016. Retargeted Selectively Replicating Adenoviruses in Combination with Antiangiogenic Therapy for the Therapy of Colon Cancer
Authors: Krisztian Homicsko, Alexander Lukashev, Richard Iggo
Journal: Molecular Therapy (2005)

In virtually all colon cancer cell lines |[beta]|-catenin is activated. The target genes of |[beta]|-catenin are activated through the interaction of |[beta]|-catenin with the transcription factor TCF. Previously in our laboratory conditionally replicating adenoviruses with TCF sites in the early viral promoters were constructed. We inserted TCF sites into the E1A, E1B and E4 promoters. This virus, vKH1, shows 1000 fold selectivity for colon cancer cell lines compared to wild type Ad5.
Over There the Sun Shines
Authors: John Graber
Journal: JAMA (2007)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 3212: Ganoderma lucidum (Reishi) chemosensitizes EGFR-overexpressing inflammatory breast cancer cells to erlotinib
Authors: Ivette Suárez-Arroyo, Michael Moraskie, Luis A. Cubano, Michelle M. Martínez-Montemayor
Journal: Cancer Research (2014)

Abstract Inflammatory Breast Cancer (IBC) is an aggressive cancer with a unique ability of forming tumor spheroids, which invade the dermal lymphatics causing the inflammatory phenotype. IBC cell lines and human tissues, overexpress Epidermal Growth Factor Receptor (EGFR), which has been associated with increasing IBC tumor growth rate, invasion and metastasis. Among the current therapeutic strategies for EGFR inhibition are the small molecule Tyrosine Kinase Inhibitors (TKIs). The high incidence of resistance to such therapies has greatly diminished their overall effectiveness, thus it seems feasible to identify agents that may be combined with these TKIs to provide a sustained response for IBC patients. For this reason, the purpose of this study is to investigate Reishi's therapeutic potential in IBC, focusing on the regulation of the EGFR signaling cascade and its contribution to the IBC cellular response when treated with the EGFR TKI, erlotinib. Our hypothesis is that Reishi sensitizes IBC cells to erlotinib therapy. EGFR-overexpressing SUM-149 IBC cells were treated with several concentrations of erlotinib, 0.025mg/mL Reishi, or both treatments simultaneously for 72h. Our results showed a synergistic effect when erlotinib and Reishi are used simultaneously after 72 hours of treatment. In order to study the molecular mechanism for the improved effects of the combination treatment we successfully developed an IBC erlotinib resistant cell line from the parental SUM-149 cells. Our data revealed that Reishi increases erlotinib sensitivity by inactivating AKT and extracellular signal-regulated kinase (ERK) signaling pathways. Taken together, our results provide evidence that Reishi chemosensitizes IBC cells to erlotinib therapy, highlighting its anti-IBC-therapeutic potential. This project was sponsored by NIH/NCI #1F31 CA174307 to ISA, Title V PPOHA US Department of Education #P031M105050 to UCC, NIH/RCMI #G12 MD007583 to UCC, NIH/INBRE #5P20 GM103475 to UPR/UCC and a research donation from the Commonwealth of Puerto Rico to UCC's University Center of Integral and Complementary Medicine (CUMIC)/MMM. Citation Format: Ivette Suárez-Arroyo, Michael Moraskie, Luis A. Cubano, Michelle M. Martínez-Montemayor. Ganoderma lucidum (Reishi) chemosensitizes EGFR-overexpressing inflammatory breast cancer cells to erlotinib. [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 3212. doi:10.1158/1538-7445.AM2014-3212
Abstract P6-07-12: Should adjuvant zoledronic acid be used in early-stage, endocrine-sensitive breast cancer?
Authors: NWD Lamond, C Skedgel, D Rayson, T Younis
Journal: Cancer Research (2013)

Abstract Introduction: Adjuvant zoledronic acid (ZA) appears to improve disease-free survival (DFS) in women with endocrine-sensitive breast cancer and low estrogen levels (LEL) including post-menopausal women, and pre-menopausal women treated with LHRH agonists. ZA, however, is also associated with potential adverse events and incremental drug acquisition costs. An overall assessment of the long-term clinical and economic impacts of adjuvant ZA may therefore help guide the decision to adopt this novel therapeutic option. We examined the incremental quality-adjusted life-years (QALY) and costs per QALY associated with adjuvant treatment including ZA relative to treatment without ZA in women with endocrine-sensitive breast cancer and LEL. Methods: A Markov model was developed to compute cumulative costs, from a Canadian perspective, and QALY associated with and without adjuvant ZA over a 25-year horizon. Costs, utilities, DFS and adverse events were derived from relevant clinical trials, the literature and local resources. One-way and probabilistic sensitivity analyses were conducted for key model parameters. Results: Adjuvant ZA was associated with incremental QALY gains of 0.62 and 0.42 and resultant CU estimates of $12,617 and $19,775 per QALY gained in pre- and post-menopausal women, respectively. CU estimates were robust across reasonable uncertainty ranges in all parameters. Conclusions: Adjuvant ZA appears to be associated with long-term QALY gains in women with endocrine-sensitive breast cancer and LEL as well as CU estimates that are below commonly accepted North American thresholds. The favourable long-term clinical and economic impacts observed in this study further support the use of adjuvant ZA in this setting. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-07-12.
Minimal important difference of the transition dyspnoea index in a multinational clinical trial
Authors: T.J. Witek, D.A. Mahler
Journal: European Respiratory Journal (2003)

Dyspnoea is a primary symptom of chronic obstructive pulmonary disease (COPD). The baseline (BDI) and transition (TDI) dyspnoea indices are commonly used instruments to assess breathlessness and the impact of intervention. Its validity and pattern of response in multinational clinical trials has not been established. In a retrospective analysis of a cohort of 997 COPD patients who received tiotropium, salmeterol or placebo, in addition to usual care, the validity and pattern of response of the BDI and TDI were examined. The BDI was significantly correlated with the dyspnoea diary (DD) score and the symptom and activity components of the St. George's respiratory questionnaire (SGRQ), establishing concurrent validity. Furthermore, the TDI was also correlated with the changes in DD, SGRQ symptom and activity scores. Construct validity was established by the association between baseline forced expiratory volume in one second (FEV 1 ) and BDI and ΔFEV 1 with TDI. Physician's global evaluation (PGE) was significantly associated with BDI as well as ΔPGE with TDI. Significant correlations have also been observed when the cohorts were classified according to native English and native non­English speaking countries. A change in PGE of 1 category ( i.e. 2 units on an 8‐point scale) was associated with a mean TDI of ∼1 unit (0.9–1.3 mean focal score), lending further support to the clinical significance of this change inherent in the instrument's descriptors. TDI responders ( i.e. focal score ≥1 unit) used less supplemental salbutamol, had fewer exacerbations and had significantly improved health status as measured by impacts and total SGRQ scores compared with nonresponders. In conclusion, the transition dyspnoea index is a valid instrument when used in a multinational clinical trial and the patterns of response confirm a 1‐unit change in the transition dyspnoea index focal score as being clinically important.
Primary Human Herpesvirus 6 Infection in Young Children
Authors: Prasong Pruksananonda, Caroline Breese Hall, Richard A. Insel, Kim McIntyre, Philip E. Pellett, Christine E. Long, Kenneth C. Schnabel, Patricia H. Pincus, Felicia R. Stamey, Timothy R. Dambaugh, John A. Stewart
Journal: New England Journal of Medicine (1992)

Human herpesvirus 6 (HHV-6) is a recently discovered virus that, on the basis of serologic evidence, appears to infect most children by the age of three years. However, the clinical manifestations of primary HHV-6 infection have not been well defined.
MENTAL DISORDER AND INTESTINAL SEPSIS
Authors: C. Joyner
Journal: BMJ (1930)

MEIA_ORLsubstance is thlrown off.Somle reaches the lymphatics, whlticlh becomie blocked, and pap)illonatosis develops.Some also ieaclies the livel, and( we xwill see a local hyp)crplasia coacurrent wvithi chironiic toxic absCrlptioIl.Ini the possessioii of thle three essential prol)erties lies the only spec,-ificity aImlioing earciniogeinetic agents.Wlhere 1o 0-e see the p)llsico-clhemlical cause at workl?In rilu ophiion it is operative in'all cases, except ill the ve'yr small anid special groups of tlhe mialign.antblastoinia-for examl)le, reiial-of early chlildlhood, anid the melanio-carci-
Howard Michael Parsons
Authors: L. Parsons
Journal: BMJ (2010)

Born to a family of butchers at home in Paddington, London, during a Zeppelin raid, Howard Michael Parsons (“Michael”) went to school at Radley College and qualified MRCS, LRCP from University College Hospital, London, in July 1942. He was one of the medical students taken to Cardiff by Professor Max Rosenheim to fast track their training during the second world war. He initially joined the Royal Army Medical Corps but soon was recruited into the Long Range Desert Group (LRDG) and saw active service as medical officer in North Africa and Italy. He was proud of belonging to the LRDG and wrote home to his father detailing his service in Albania, where he was parachuted in at dead of night to treat …
Sir Frederic Bartlett Lectureship
Authors: L. Weiskrantz, O. L. Zangwill
Journal: BMJ (1965)

<h3>Background</h3> Few studies have compared technical success and effectiveness of transradial access (TRA) versus transfemoral access (TFA) for mechanical thrombectomy (MT) for acute ischemic stroke (AIS). We compared the two approaches for technical success, effectiveness, and outcomes. <h3>Methods</h3> We retrospectively compared TRA with TFA for AIS MT at our institute. We additionally performed a systematic review and meta-analysis of studies describing the use of TRA alone or in comparison with TFA for MT. Primary outcomes included rate of successful reperfusion (thrombolysis in cerebral infarction (TICI) &gt;2b), number of passes, access-site complications, and 3- month mortality and favorable functional outcomes (modified Rankin Scale (mRS) score 0–2). <h3>Results</h3> A total of 222 consecutive patients (TRA=93, TFA=129) were included in our case series. The rate of successful reperfusion was significantly higher for the TFA cohort (91.4% vs 79.6%, P=0.01) with lower mean number of passes (1.8±1.2 vs 2.4±1.6, P=0.014). Three-month mortality in the TFA group was lower (22.1% vs 40.9% for the TRA cohort (P=0.004), with a higher rate of favorable functional outcomes (51.3% vs 34.1%, P=0.015). A meta-analysis of 10 studies showed significant heterogeneity in rates of successful reperfusion (57.1% to 95.6%, heterogeneity=67.55%, P=0.001). None of the previous comparative studies reported 3-month mortality and functional outcomes. <h3>Conclusions</h3> This case series demonstrate a higher successful reperfusion rate, fewer passes, lower 3-month mortality, and improved 3-month functional outcomes with TFA. The systematic review highlights the inadequacy of existing evidence. Prospective comparative studies are needed before a ‘radial-first’ approach can be adopted for stroke intervention.