tbuckley/cabot-search huggingface dataset:
432. Safety of Administration of AAV2CUhCLN2, a Candidate Treatment for Late Infantile Neuronal Lipofuscinosis to the Brain of Rats and Non-Human Primates
Authors: Michael J. Blankinship, Paul Gregorevic, Jeffrey S. Chamberlain
Journal: Molecular Therapy (2004)

Vectors based on recombinant adeno-associated virus (rAAV) have garnered significant interest in gene replacement therapies for Duchenne muscular dystrophy. Several serotypes of rAAV have been shown to transduce skeletal muscle with high efficiency and low toxicity. These vectors suggest a possible therapeutic approach where dystrophin expression cassettes could be delivered to the striated musculature of an affected individual. However, a significant constraint inherent in rAAV vectors is their relatively small packaging capacity of approximately 5 kb. This packaging capacity is of great concern in attempting to deliver dystrophin via rAAV as the dystrophin cDNA is approximately 14 kb. This limitation has been overcome by engineering dystrophin proteins encompassing large deletions, which nonetheless remain highly functional. An additional concern in gene replacement therapies is the possibility of a patient's immune system viewing the therapeutic protein as a foreign antigen and raising a detrimental immune response, as the patient may not normally express the therapeutic protein. In Duchenne muscular dystrophy, a possible alternative to dystrophin replacement is utrophin over-expression. Utrophin is an autosommal homologue of dystrophin that is expressed in patients and should be viewed as a self antigen. Utrophin over-expression has been shown to functionally rescue a dystrophin deficient mouse model of muscular dystrophy, though the utrophin cDNA is also too large to be packaged into rAAV vectors without modification. Here we report and characterize a micro-utrophin protein based precisely on our previously reported, highly functional micro-dystrophin (ΔR4-R23/ ΔCT). Despite high, uniform expression and proper localization to the sarcolemma, this protein is not as efficient as micro-dystrophin in rescuing the dystrophic phenotype. Significant pathology is seen on a gross histological level despite restoration of DGC proteins to the sarcolemma. These findings highlight potential difficulties in micro-utrophin based therapies for Duchenne muscular dystrophy via rAAV, and suggest that domain engineering may be required to enable generation of a functional micro-utrophin/dystrophin hybrid.
Immune‐Mediated Paraneoplastic Neurologic Disorders: An Overview
Authors: Myrna R. Rosenfeld, Josep Dalmau
Journal: Neuro-Oncology (2012)

Paraneoplastic neurologic disorders (PND) are cancer-associated neurologic disorders resulting from a variety of pathogenic mechanisms. This chapter focuses on PND that are known or suspected to be immune-mediated. The autoimmune etiology is supported by the detection in serum and cerebrospinal fluid of antibodies that react with neuronal antigens, the presence of inflammatory cells in the cerebrospinal fluid, clinical response to immunomodulatory therapies, and studies demonstrating the pathogenic effect of some antibodies.
Abstract #LB-290: Multi-color in vivo targeted imaging to guide real-time surgery of HER2-positive micro-metastases in a two-tumor coincident model of ovarian cancer
Authors: Michelle Longmire, Nobuyuki Kosaka, Mikako Ogawa, Peter Choyke, Hisataka Kobayashi
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Introduction One goal of oncologic molecular imaging is to accurately identify and characterize malignant tissues in vivo . One approach to increasing the specificity of molecular imaging in cancer is to employ multiple probes, each with distinct fluorescence, to target several surface antigens simultaneously, permitting tissue identification based on an expression profile of multiple molecules unique to disease, rather than relying on a single target. Characterization of tissue using multicolor fluorescence will require the accurate and simultaneous identification of several optical probes in vivo . Methods We conducted a series of experiments to evaluate the ability of real-time multicolor imaging for tissue characterization based on fluorescence properties. To do so, we created a unique \#8220;coincident\#8221; tumor mouse model of disease in which animals were inoculated with tumors from two different ovarian cancer cell lines resulting in two distinct and occasionally \#8220;coincident\#8221; phenotypes. The \#8220;coincident\#8221; ovarian cancer mouse model was created by separately injecting mice with HER2+/RFP- SKOV3 and HER2-/RFP+ SHIN3-RFP. The HER2 receptor of the SKOV3 cell line was targeted with trastuzumab-rhodamine green to create green tumor implants, while the RFP plasmid of the SHIN3 cells created red tumor implants. For in situ (n=5) and in vivo experiments (n=5), intra-abdominal tumor implants were excised from anesthetized mice using real-time multicolor imaging for guidance. In both sets of experiments, tumors implants were imaged using real-time multicolor imaging, excised and categorized according to fluorescence. Sensitivity and specificity was then determined by sorting tumor nodules according to fluorescence, using multi-spectral imaging. Results Analysis of in situ tissue data revealed that real-time multicolor optical imaging was both sensitive (n=5, 90±7.6%) and specific (n=5, 90±8.2%) for the detection of HER2+ tumors. Analysis of in vivo tissue sampling revealed that real-time multicolor optical imaging was again both was both sensitive (n=5, 96±4.0%) and specific (n=5, 96±3.4%). Conclusion We have demonstrated that real-time multicolor imaging enables accurate identification of fluorescence properties of probe-targeted tissue and that fluorescence characteristics can then serve as an accurate intraoperative guide for the removal of disease. 

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-290.
Detection of abnormal pretransplant clones in progenitor cells of patients who developed myelodysplasia after autologous transplantation
Authors: Elisabetta Abruzzese, James E. Radford, Jeffrey S. Miller, James J. Vredenburgh, P. Nagesh Rao, Mark J. Pettenati, Julia M. Cruz, James J. Perry, Sergio Amadori, David D. Hurd
Journal: Blood (1999)
Myoglobin, creatine-kinase-MB and cardiac troponin-I 60-minute ratios predict infarct-related artery patency after thrombolysis for acute myocardial infarction
Authors: Milenko J Tanasijevic, Christopher P Cannon, Elliott M Antman, Donald R Wybenga, George A Fischer, Christine Grudzien, C.Michael Gibson, James W Winkelman, Eugene Braunwald
Journal: Journal of the American College of Cardiology (1999)
HEP versus PNU Standardization of Allergen Extracts in Skin Prick Testing
Authors: A. Dirksen, H.‐J. Mallinc, H. Mosbech, M. Søborg, I. Biering
Journal: Allergy (1985)

During 1 year, all patients referred to an allergy outpatient clinic for adults were skin prick tested with a panel of standard allergen extracts from two manufacturers using different methods of standardization. One company referred to the histamine equivalent prick (HEP) and the other used the more traditional protein nitrogen units (PNU). Standard extracts and five-fold dilution were tested. The results indicate that the ratio of concentration between two extracts of the same allergen should be measured by the absolute difference of the wheal diameters. We found significant differences between corresponding extracts from the two manufacturers.
Apolipoprotein E and Progression of Chronic Kidney Disease
Authors: Yujiro Kida
Journal: JAMA (2006)

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
Experts Debate Widening Use of Opioid Drugs for Chronic Nonmalignant Pain
Authors: Mike Mitka
Journal: JAMA (2003)

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
Treatment of respiratory allergy with allergy immunotherapy tablets
Authors: C. Bachert
Journal: Allergy (2011)

Allergy immunotherapy tablets (AIT) have expanded the treatment options for patients suffering from respiratory allergies. Efficacy is established in adults and children for two different commercially available grass AITs. The ALK grass AIT has an efficacy comparable to subcutaneous immunotherapy (SCIT), with a proven disease-modifying effect after treatment completion. Safety profiles favour AIT over SCIT. Studies suggest that tablets in all aspects are superior to sublingual drops. AITs for other allergies including house dust mite and birch and ragweed pollen are in development.
Older women should receive annual breast examinations
Authors: R. M. de Souza, V. M de Souza
Journal: BMJ (1998)

EDITOR—Haigney et al have reported the results of a questionnaire survey of breast cancer screening practices in older women.1 The study emphasised the conflict between knowledge of the recommended cancer screening tests and doctors' actual practice. Some methodological aspects regarding the results were not discussed, such as the possibility of selection bias with respect to the hospital doctors interviewed (response rate 75%). The study raises the issue that despite knowing what they should do …
Erratum: Genome-wide association identifies multiple ulcerative colitis susceptibility loci
Authors: Dermot P B McGovern, Agnès Gardet, Leif Törkvist, Philippe Goyette, Jonah Essers, Kent D Taylor, Benjamin M Neale, Rick T H Ong, Caroline Lagacé, Chun Li, Todd Green, Christine R Stevens, Claudine Beauchamp, Phillip R Fleshner, Marie Carlson, Mauro D'Amato, Jonas Halfvarson, Martin L Hibberd, Mikael Lördal, Leonid Padyukov, Angelo Andriulli, Elisabetta Colombo, Anna Latiano, Orazio Palmieri, Edmond-Jean Bernard, Colette Deslandres, Daan W Hommes, Dirk J de Jong, Pieter C Stokkers, Rinse K Weersma, Yashoda Sharma, Mark S Silverberg, Judy H Cho, Jing Wu, Kathryn Roeder, Steven R Brant, L Phillip Schumm, Richard H Duerr, Marla C Dubinsky, Nicole L Glazer, Talin Haritunians, Andy Ippoliti, Gil Y Melmed, David S Siscovick, Eric A Vasiliauskas, Stephan R Targan, Vito Annese, Cisca Wijmenga, Sven Pettersson, Jerome I Rotter, Ramnik J Xavier, Mark J Daly, John D Rioux, Mark Seielstad
Journal: Nature Genetics (2011)
Vascular cell adhesion molecule 1 expression by biliary epithelium promotes persistence of inflammation by inhibiting effector T-cell apoptosis
Authors: Simon C. Afford, Elizabeth H. Humphreys, Danielle T. Reid, Clare L. Russell, Vanessa M. Banz, Ye Oo, Tina Vo, Craig Jenne, David H. Adams, Bertus Eksteen
Journal: Hepatology (2013)

Chronic hepatitis occurs when effector lymphocytes are recruited to the liver from blood and retained in tissue to interact with target cells, such as hepatocytes or bile ducts (BDs). Vascular cell adhesion molecule 1 (VCAM-1; CD106), a member of the immunoglobulin superfamily, supports leukocyte adhesion by binding α4β1 integrins and is critical for the recruitment of monocytes and lymphocytes during inflammation. We detected VCAM-1 on cholangiocytes in chronic liver disease (CLD) and hypothesized that biliary expression of VCAM-1 contributes to the persistence of liver inflammation. Hence, in this study, we examined whether cholangiocyte expression of VCAM-1 promotes the survival of intrahepatic α4β1 expressing effector T cells. We examined interactions between primary human cholangiocytes and isolated intrahepatic T cells ex vivo and in vivo using the Ova-bil antigen-driven murine model of biliary inflammation. VCAM-1 was detected on BDs in CLDs (primary biliary cirrhosis, primary sclerosing cholangitis, alcoholic liver disease, and chronic hepatitis C), and human cholangiocytes expressed VCAM-1 in response to tumor necrosis factor alpha alone or in combination with CD40L or interleukin-17. Liver-derived T cells adhered to cholangiocytes in vitro by α4β1, which resulted in signaling through nuclear factor kappa B p65, protein kinase B1, and p38 mitogen-activated protein kinase phosphorylation. This led to increased mitochondrial B-cell lymphoma 2 accumulation and decreased activation of caspase 3, causing increased cell survival. We confirmed our findings in a murine model of hepatobiliary inflammation where inhibition of VCAM-1 decreased liver inflammation by reducing lymphocyte recruitment and increasing CD8 and T helper 17 CD4 T-cell survival. Conclusions : VCAM-1 expression by cholangiocytes contributes to persistent inflammation by conferring a survival signal to α4β1 expressing proinflammatory T lymphocytes in CLD. (Hepatology 2014;59:1932–1943)
Sustained generation and survival of antigen-specific CD62Lhigh CD8+ T-cells through in vitro conditioning with interleukin-12: Implications for anti-tumor adoptive immunotherapy.
Authors: C. Marcela Diaz-Montero, Andre Kadima, Sabry A. El-Naggar, Narender Nath, David J. Cole, Mohamed L. Salem
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5578 

Recent adoptive immunotherapy studies have shown that the anti-tumor effects of in vitro expanded antigen-specific CD62LhighCD8+ effector T cells, followed by antigen vaccination, are superior to that of CD62LlowCD8+ T cells. Thus, maintaining the expression of CD62L in activated CD8+ T cells is desirable for the induction of effective anti-tumor immunity. Several recent studies have focused on factors that can augment proliferation, increase survival, and sustain CD62L expression on effector memory CD8+ T cells. We and others have previously reported on the adjuvant role of IL-12 in different vaccine settings. However, little is known about the impact of this potent adjuvant cytokine on the generation of CD62Lhigh CD8+ effector T cells. In this study, we aimed to test the capability of IL-12 to generate less apoptotic CD8+ T cells with a CD62Lhigh phenotype. To address this hypothesis, we stimulated TCR transgenic (OT-1) CD8+ T cells, which recognize MHC class-I (SIINFEKL) OVA peptide, with peptide-pulsed syngenic spleen cells for 3 days and then CD8+ T cells were washed, enriched, and recultured in fresh medium for another 4 days. IL-12 (10 ng/ml) was added either immediately or after 3 days of priming. Our results clearly show that addition of IL-12 immediately, as a 3rd signal, or 3 days after priming of enriched CD8+ T cells, as a survival factor, skewed the majority of antigen-specific CD8+ T cells to CD62Lhigh phenotype (>90% with IL-12 versus 20% with no IL-12). Importantly, >95% of these cells were able to survive until day 6 post-priming. These effects were unique for IL-12, as treatment with IL-23, which shares IL-12Rβ1, either alone or in combination with IL-17 which is induced by IL-23, had no effect on the proliferation or survival of CD62Lhigh CD8+ . In conclusion, treatment of antigen-primed CD8+ T cells with IL-12 is a potential approach to generate and improve survival of CD62Lhigh population. This finding has important implications for anti-tumor adoptive immunotherapy and subsequent active vaccination.
A course that changed my curriculum vitae: The pen is mightier than the sword
Authors: C. Essex
Journal: BMJ (1999)

I had been qualified eight years before my first article was published. Over the next few years I got a handful of articles into print, mostly in the popular sections of the BMJ such as the Personal view column or the now defunct Materia non medica column. I even got paid £25 for a piece in another journal's Mea Culpa section. I thought that I might make a healthy living as a regular contributor to that column.

But I was getting too many rejection slips until I went on a weekend medical writing course. The medical journalist running the course …
Heavy Night Call vs Alcohol Ingestion in Residents
Authors: Daniel Merenstein
Journal: JAMA (2006)

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
Efficacy of Vinblastine in Primary Cutaneous Anaplastic Large Cell Lymphoma
Authors: Pauline Laly, Saskia Ingen-Housz-Oro, Marie Beylot-Barry, Laurence Verneuil, Henri Adamski, Pauline Brice, Martine Bagot
Journal: JAMA Dermatology (2015)

Anaplastic Large Cell LymphomaPrimary cutaneous anaplastic large cell lymphoma (C-ALCL) is a rare primary cutaneous CD30 + T-cell lymphoproliferative disorder that affects patients at a median age of 60 years.The disease presents as localized or less frequently disseminated nodules, plaques, or ulcers that mostly affect limbs.Prognosis is favorable (5-year overall survival, >80%).According to the consensus recommendations, 1 surgical excision or radiotherapy is recommended for localized lesions.For multifocal lesions, low-dose methotrexate is commonly used with a favorable response. 2Multiagent chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, is effective but because of adverse effects and a high rate of relapses is reserved for disseminated relapse and extracutaneous dissemination. 1 Brentuximab vedotin has excellent effectiveness, 3 but its use remains off label, expensive, and sometimes responsible for neuropathy and severe infectious complications.Consequently, therapeutic recommendations are lacking for patients with methotrexate failure, especially for older patients.We report a series of 7 patients who received vinblastine as single-agent chemotherapy for relapsing multifocal C-ALCL.
Global impact of an educational antimicrobial stewardship programme on prescribing practice in a tertiary hospital centre
Authors: J.M. Cisneros, O. Neth, M.V. Gil-Navarro, J.A. Lepe, F. Jiménez-Parrilla, E. Cordero, M.J. Rodríguez-Hernández, R. Amaya-Villar, J. Cano, A. Gutiérrez-Pizarraya, E. García-Cabrera, J. Molina
Journal: Clinical Microbiology and Infection (2013)
Factors associated with bronchiolitis obliterans syndrome and chronic graft‐versus‐host disease after allogeneic hematopoietic cell transplantation
Authors: Lee Gazourian, Angela J. Rogers, Ruby Ibanga, Gerald L. Weinhouse, Victor Pinto‐Plata, Jerome Ritz, Robert J. Soiffer, Joseph H. Antin, George R. Washko, Rebecca M. Baron, Vincent T. Ho
Journal: American Journal of Hematology (2013)

Bronchiolitis obliterans syndrome (BOS) is a form of chronic graft vs. host disease (cGVHD) and a highly morbid pulmonary complication after allogeneic hematopoietic stem cell transplantation (HSCT). We assessed the prevalence and risk factors for BOS and cGVHD in a cohort of HSCT recipients, including those who received reduced intensity conditioning (RIC) HSCT. Between January 1, 2000 and June 30, 2010, all patients who underwent allogeneic HSCT at our institution (n = 1854) were retrospectively screened for the development of BOS by PFT criteria. We matched the BOS cases with two groups of control patients: (1) patients who had concurrent cGVHD without BOS and (2) those who developed neither cGVHD nor BOS. Comparisons between BOS patients and controls were conducted using t-test or Fisher's exact tests. Multivariate regression analysis was performed to examine factors associated with BOS diagnosis. All statistical analyses were performed using SAS 9.2. We identified 89 patients (4.8%) meeting diagnostic criteria for BOS at a median time of 491 days (range: 48-2067) after HSCT. Eighty-six (97%) of our BOS cohort had extra-pulmonary cGVHD. In multivariate analysis compared to patients without cGVHD, patients who received busulfan-based conditioning, had unrelated donors, and had female donors were significantly more likely to develop BOS, while ATG administration was associated with a lower risk of BOS. Our novel results suggest that busulfan conditioning, even in RIC transplantation, could be an important risk factor for BOS and cGVHD.