tbuckley/cabot-search huggingface dataset:
Control of lung defence by mucins and macrophages: ancient defence mechanisms with modern functions
Authors: William J. Janssen, Adrianne L. Stefanski, Bruce S. Bochner, Christopher M. Evans
Journal: European Respiratory Journal (2016)

Owing to the need to balance the requirement for efficient respiration in the face of tremendous levels of exposure to endogenous and environmental challenges, it is crucial for the lungs to maintain a sustainable defence that minimises damage caused by this exposure and the detrimental effects of inflammation to delicate gas exchange surfaces. Accordingly, epithelial and macrophage defences constitute essential first and second lines of protection that prevent the accumulation of potentially harmful agents in the lungs, and under homeostatic conditions do so effectively without inducing inflammation. Though epithelial and macrophage-mediated defences are seemingly distinct, recent data show that they are linked through their shared reliance on airway mucins, in particular the polymeric mucin MUC5B. This review highlights our understanding of novel mechanisms that link mucus and macrophage defences. We discuss the roles of phagocytosis and the effects of factors contained within mucus on phagocytosis, as well as newly identified roles for mucin glycoproteins in the direct regulation of leukocyte functions. The emergence of this nascent field of glycoimmunobiology sets forth a new paradigm for considering how homeostasis is maintained under healthy conditions and how it is restored in disease.
Cholesterol and Coronary Heart Disease Risk in Elderly Patients-Reply
Authors: Stephen B. Hulley
Journal: JAMA (1995)

In Reply.  —Dr Harris and colleagues note that busy practitioners may be left with the impression that lipoprotein lipids are not risk factors for older people. This would be rational, since this is the empirical observation. We do agree with Harris et al that the paradoxical inverse association between blood cholesterol and mortality, which extends to the upper half of the cholesterol distribution in the elderly, 1 may not be causal. Their hypothesis that this association would go the other way were it not for an interaction with prior health status is intriguing, but only one of the possible explanations, only partly supported in their own studies, 2 and still to be examined elsewhere.  Two other issues raised by Harris et al deserve comment. One is their use of the LaRosa et al reference, from which they concluded that lipid treatment is not hazardous in the elderly. That was a
Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming
Authors: María E. Rodriguez-Ruiz, Inmaculada Rodriguez, Saray Garasa, Benigno Barbes, Jose Luis Solorzano, Jose Luis Perez-Gracia, Sara Labiano, Miguel F. Sanmamed, Arantza Azpilikueta, Elixabet Bolaños, Alfonso R. Sanchez-Paulete, M. Angela Aznar, Ana Rouzaut, Kurt A. Schalper, Maria Jure-Kunkel, Ignacio Melero
Journal: Cancer Research (2016)

Abstract Preclinical and clinical evidence indicate that the proimmune effects of radiotherapy can be synergistically augmented with immunostimulatory mAbs to act both on irradiated tumor lesions and on distant, nonirradiated tumor sites. The combination of radiotherapy with immunostimulatory anti-PD1 and anti-CD137 mAbs was conducive to favorable effects on distant nonirradiated tumor lesions as observed in transplanted MC38 (colorectal cancer), B16OVA (melanoma), and 4T1 (breast cancer) models. The therapeutic activity was crucially performed by CD8 T cells, as found in selective depletion experiments. Moreover, the integrities of BATF-3–dependent dendritic cells specialized in crosspresentation/crosspriming of antigens to CD8+ T cells and of the type I IFN system were absolute requirements for the antitumor effects to occur. The irradiation regimen induced immune infiltrate changes in the irradiated and nonirradiated lesions featured by reductions in the total content of effector T cells, Tregs, and myeloid-derived suppressor cells, while effector T cells expressed more intracellular IFNγ in both the irradiated and contralateral tumors. Importantly, 48 hours after irradiation, CD8+ TILs showed brighter expression of CD137 and PD1, thereby displaying more target molecules for the corresponding mAbs. Likewise, PD1 and CD137 were induced on tumor-infiltrating lymphocytes from surgically excised human carcinomas that were irradiated ex vivo. These mechanisms involving crosspriming and CD8 T cells advocate clinical development of immunotherapy combinations with anti-PD1 plus anti-CD137 mAbs that can be synergistically accompanied by radiotherapy strategies, even if the disease is left outside the field of irradiation. Cancer Res; 76(20); 5994–6005. ©2016 AACR.
구연 : 경동맥 화학 색전술로 완전 괴사된 간세포암 환자의 추적 관찰 방법에 따른 무병 생존율의 비교; 컴퓨터 단층 촬영과 혈관 조영술 후 컴퓨터 단층 촬영
Authors: 장명국, 이한주, 신정우, 김인숙, 김성훈, 최원범, 임영석, 정영화, 이영상, 서동진, 성규보, 윤현기, 고기영
Journal: Clinical and Molecular Hepatology (2003)

배경/목적: 경동맥 화학색전술(TACE)은 환자의 생존을 증가시키는 것으로 알려져 있다. 그러나 완전 괴사후의 추적 관찰 방법에 대해서는 일치된 의견이 없다. 비침습적이고 효과적인 추적 관찰 방법을 제시하고자 본 연구를 시행하였다. 대상과 방법: 2000년 10월부터 2001년 10월 사이에 간세포암으로 진단받고 TACE를 시행받은 192명 중 1개월 후 추적 관찰한 컴퓨터 단층 촬영(CT)에서 완전 관해가 확인된 70명(36%)의 연속된 환자를 대상으로 하였다. 환자는 교대로 CT군(36명)과 ANGIO군(34명)으로 분류하였다. CT군에서는 3개월 간격으로 CT만으로 추적관찰하고 ANGIO군에서는 1개월후 혈관촬영으로 완전관해를 재확인하고 이후 3개월 간격으로 CT를 이용해 추적관찰하였다. 결과: 1) 양 군의 인구학적, 생화학적 특성 및 기저 간질환과 간세포암의 특성은 유사하였다. 2) ANGIO군의 5명(15%)에서 추가 혈관 촬영상 잔여 생존암이 의심(3명, 9%), 혹은 확인(2명, 6%)되었다. 3) 양군간의 전체 생존율 및 무병 생존율(그림)에는 유의한 차이가 없었다. 3) ANGIO군의 79%(27명)에서 적어도 한가지 이상의 합병증이 발생하였으며 간기능이상이 32%(11명), 신기능이상이 2명(6%)에서 혈관촬영술 시행 24시간 이내에 관찰되었다.
(표) : 
결론: TACE로 역동적 CT상 완전 괴사가 얻어진 경우 이를 확인하기 위한 추가 혈관 촬영은 불필요하며 정기적인 역동적 CT 추적으로 충분할 것으로 생각된다.
Efficacy and safety of the combination of lapatinib plus capecitabine for HER2-positive advanced breast cancer.
Authors: E. Aravantinou-Fatorou, C. Christodoulou, A. Nikolakopoulou, E. Galani, G. Klouvas, V. Acholos, G. Karapanagiotidis, E. Batziou, G. Tsakalos, D. Skarlos
Journal: Journal of Clinical Oncology (2010)

e11520 Background: Effective treatment options for patients with metastatic breast cancer resistant to anthracyclines, taxanes and trastuzumab are limited. Lapatinib, an oral receptor tyrosine kinase inhibitor, targeting both the human epidermal growth factor receptor type 2 (HER2) and epidermal growth factor receptor (EGFR), is active in combination with capecitabine in women with HER2-positive advanced breast cancer. The retrospective study purpose is to assess the safety and efficacy of the 21-day schedule of lapatinib plus capecitabine in a nonselected population, as applied in the every-day practice of our department. Methods: We retrospectively reviewed data from 27 patients treated with lapatinib at a dose of 1,250 mg per day continuously plus capecitabine at a dose of 2,000 mg per square meter of body surface area on days 1 through 14 of a 21-day cycle from June 2007 to January 2010. It is of interest that this group of patients was heavily pretreated with taxanes (100%), anthacyclines (74%), trastuzumab (81%), and other chemotherapeutic drugs. They had received median 4 prior lines of chemotherapy for metastatic breast cancer. Results: Complete response (CR) was achieved in 2 patients (8%), partial response (PR) in 9 (33%), and stable disease (SD) in 3 (11%). The median time to progression was 23 weeks and the overall survival 73 weeks. The most common adverse events were diarrhea, vomiting, hand and foot syndrome, fatigue, and rash. Most adverse events were grade I and II. Grade III toxicities included diarrhea (11%), fatigue (4%), hand and foot syndrome (8%), vomiting (4%), and instability (4%). No toxic death occurred. Conclusions: The 21-day schedule was well tolerated and effective in heavily-pretreated women with HER2-positive advanced breast cancer. No significant financial relationships to disclose.
Increased Functional T Cell Defects in Patients with low CD4 Counts after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Udo Holtick, Lukas P. Frenzel, Shimabukuro-Vornhagen Alexander, Sebastian Theurich, Julia Claasen, Christof Scheid, Michael von-Bergwelt-Baildon, Michael Hallek, Clemens Wendtner, Jens M. Chemnitz
Journal: Blood (2013)
It’s Rough Out There for Us
Authors: Michael D. Stillman, Steve R. Williams
Journal: JAMA (2016)

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
Anti-CXCL12/SDF-1 Spiegelmer® Nox-A12 Alone and In Combination With Bortezomib and Dexamethasone In Patients With Relapsed Multiple Myeloma: Results From A Phase IIa Study
Authors: Heinz Ludwig, Katja Weisel, Monika Engelhardt, Richard Greil, Anna Maria Cafro, Maria Teresa Petrucci, Thomas Dümmler, Stefan Zöllner, Stefan Zeitler, Kai Riecke, Anna Kruschinski
Journal: Blood (2013)
In Vivo Gene Delivery to Lymph Node Stromal Cells Leads to Transgene-specific CD8+ T Cell Anergy in Mice
Authors: Séverine Ciré, Sylvie Da Rocha, Maxime Ferrand, Mary K Collins, Anne Galy
Journal: Molecular Therapy (2016)

Lymph node stromal cells play a role in self-tolerance by presenting tissue antigens to T cells. Yet, immunomodulatory properties of lymphoid tissue stroma, particularly toward CD4+ T cells, remain insufficiently characterized by lack of tools to target antigens for presentation by stromal cells. A lentiviral vector was therefore designed for antigen delivery to MHC class II+ cells of nonhematopoietic origin. Following intravenous vector delivery, the transgene was detected in lymph node gp38+ stromal cells which were CD45- MHCII+ and partly positive for CD86 and CTLA4 or B7-H4. The transgene was not detected in classical dendritic cells of lymph nodes or spleen. Transgene-specific CD4+ and CD8+ T cell responses were primed and regulatory T cells were also induced but effector T cell response did not develop, even after a peptide boost. Antigen-specific CD8+ T cells were not cytolytic in vivo. Thus, expressing a neo-antigen in MHC-II+ lymph node stroma seems to trigger blunt CD4 T cell responses leading to antigen-specific CD8+ T cell anergy. These results open up new perspectives to further characterize lymph node stromal cell functional properties and to develop gene transfer protocols targeting lymph node stroma to induce peripheral tolerance.
In Chronic Myeloid Leukemia Patients on 2nd-Line Tyrosine Kinase Inhibitor Therapy, Deep Sequencing at the Time of Warning May Allow Sensitive Detection of Emerging BCR-ABL1 Mutants
Authors: Simona Soverini, Caterina De Benedittis, Luca Zazzeroni, Katerina Machova Polakova, Fausto Castagnetti, Gabriele Gugliotta, Maria Teresa Bochicchio, Ilaria Iacobucci, Marzia Salvucci, Monica Crugnola, Gianni Binotto, Massimiliano Bonifacio, Giovanna Leonardi, Alessandra Iurlo, Giorgina Specchia, Domenico Russo, Fabrizio Pane, Giuseppe Saglio, Gianantonio Rosti, Michele Cavo, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2014)
Kinase Domain Point Mutations in Ph+ Acute Lymphoblastic Leukemia (ALL) and Lymphoid Blast Crisis of Chronic Myeloid Leukemia (CML) and Their Emergence Following Therapy with Bcr-Abl Kinase Inhibitors.
Authors: Dan Jones, Rayjalakshmi Luthra, Hagop M. Kantarjian, Megan Breeden, Susan O’Brien, Stefan Faderl, Jorge Cortes, Deborah Thomas
Journal: Blood (2006)
Non-Irradiation Approach To Study Hematopoiesis and Leukemogenesis In a De Novo Murine Model Of Hematopoietic/Leukemia Stem Cell Transplant
Authors: Xiaofei Liu, Dan Yang, Shumin Fang, Yang Geng, Qianhao Zhao, Pengjie Yang, Siying Peng, Yuelei Shen, Guangjin Pan, Jinyong Wang
Journal: Blood (2013)
Natural course and prognosis of anaplastic gangliogliomas: a multicenter retrospective study of 43 cases from the French Brain Tumor Database
Authors: Louis-Marie Terrier, Luc Bauchet, Valérie Rigau, Aymeric Amelot, Sonia Zouaoui, Isabelle Filipiak, Agnès Caille, Fabien Almairac, Marie-Hélène Aubriot-Lorton, Anne-Marie Bergemer-Fouquet, Eric Bord, Philippe Cornu, Alain Czorny, Phong Dam Hieu, Bertrand Debono, Marie-Bernadette Delisle, Evelyne Emery, Walid Farah, Guillaume Gauchotte, Catherine Godfraind, Jacques Guyotat, Bernard Irthum, Kevin Janot, Pierre-Jean Le Reste, Dominique Liguoro, Hugues Loiseau, Guillaume Lot, Vincent Lubrano, Emmanuel Mandonnet, Philippe Menei, Philippe Metellus, Serge Milin, Bertrand Muckenstrum, Pierre-Hugues Roche, Audrey Rousseau, Emmanuelle Uro-Coste, Anne Vital, Jimmy Voirin, Michel Wager, Marc Zanello, Patrick François, Stéphane Velut, Pascale Varlet, Dominique Figarella-Branger, Johan Pallud, Ilyess Zemmoura
Journal: Neuro-Oncology (2016)

Anaplastic gangliogliomas (GGGs) are rare tumors whose natural history is poorly documented. We aimed to define their clinical and imaging features and to identify prognostic factors. Consecutive cases of anaplastic GGGs in adults prospectively entered into the French Brain Tumor Database between March 2004 and April 2014 were screened. After diagnosis was confirmed by pathological review, clinical, imaging, therapeutic, and outcome data were collected retrospectively. Forty-three patients with anaplastic GGG (median age, 49.4 y) from 18 centers were included. Presenting symptoms were neurological deficit (37.2%), epileptic seizure (37.2%), or increased intracranial pressure (25.6%). Typical imaging findings were unifocal location (94.7%), contrast enhancement (88.1%), central necrosis (43.2%), and mass effect (47.6%). Therapeutic strategy included surgical resection (95.3%), adjuvant radiochemotherapy (48.8%), or radiotherapy alone (27.9%). Median progression-free survival (PFS) and overall survival (OS) were 8.0 and 24.7 months, respectively. Three- and 5-year tumor recurrence rates were 69% and 100%, respectively. The 5-year survival rate was 24.9%. Considering unadjusted significant prognostic factors, tumor midline crossing and frontal location were associated with shorter OS. Temporal and parietal locations were associated with longer and shorter PFS, respectively. None of these factors remained statistically significant in multivariate analysis. We report a large series providing clinical, imaging, therapeutic, and prognostic features of adult patients treated for an intracerebral anaplastic GGG. Our results show that pathological diagnosis is difficult, that survivals are only slightly better than for glioblastomas, and that complete surgical resection followed with adjuvant chemoradiotherapy offers longer survival.
Functional Evidence from Deuterated Water Labeling That the Bruton Tyrosine Kinase Inhibitor Ibrutinib Blocks Leukemia Cell Proliferation and Trafficking and Promotes Leukemia Cell Death in Patients with Chronic Lymphocytic Leukemia and small Lymphocytic Lymphoma
Authors: Jan A. Burger, Kelvin Li, Michael Keating, Mariela Sivina, Alessandra Ferrajoli, Annette Jalayer, Xuelin Huang, Hagop M. Kantarjian, William G. Wierda, Susan O'Brien, Marc Hellerstein, Scott Turner, Claire Emson, Shih-Shih Chen, Xiao-Jie Yan, Nicholas Chiorazzi
Journal: Blood (2014)
The Presence of Alzheimer's Disease in a Community Population
Authors: Emre Kokmen
Journal: JAMA (1990)

<h3>To the Editor.—</h3> The importance and several limitations of the study by Evans et al<sup>1</sup>on Alzheimer's disease in the East Boston population were recognized in the accompanying editorial by Dr Larson.<sup>2</sup>We wish to congratulate the authors for providing additional age-specific prevalence rates for the dementias. Elucidation of geographic and population patterns of dementia is necessary to develop hypotheses related to the pathophysiology of common dementing illnesses such as Alzheimer's disease. Increasing support by the National Institute on Aging for epidemiologic studies—including those at various centers in the United States and the studies being undertaken in the Mariana Islands, which will use mainland rates as a basis for comparison—is timely and appropriate. As Evans et al point out, the difficulties of case ascertainment and uniformity of diagnosis in the ongoing studies require that they "be interpreted with caution." In the East Boston study, the diagnosis of dementia
Monitoring Marijuana Use in the United States
Authors: Alejandro Azofeifa, Margaret E. Mattson, Althea Grant
Journal: JAMA (2016)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Clinical Aspects of Type 3 Long-QT Syndrome
Authors: Arthur A.M. Wilde, Arthur J. Moss, Elizabeth S. Kaufman, Wataru Shimizu, Derick R. Peterson, Jesaia Benhorin, Coeli Lopes, Jeffrey A. Towbin, Carla Spazzolini, Lia Crotti, Wojciech Zareba, Ilan Goldenberg, Jørgen K. Kanters, Jennifer L. Robinson, Ming Qi, Nynke Hofman, David J. Tester, Connie R. Bezzina, Marielle Alders, Takeshi Aiba, Shiro Kamakura, Yoshihiro Miyamoto, Mark L. Andrews, Scott McNitt, Bronislava Polonsky, Peter J. Schwartz, Michael J. Ackerman
Journal: Circulation (2016)

Risk stratification in patients with type 3 long-QT syndrome (LQT3) by clinical and genetic characteristics and effectiveness of β-blocker therapy has not been studied previously in a large LQT3 population.The study population included 406 LQT3 patients with 51 sodium channel mutations; 391 patients were known to be event free during the first year of life and were the focus of our study. Clinical, electrocardiographic, and genetic parameters were acquired for patients from 7 participating LQT3 registries. Cox regression analysis was used to evaluate the independent contribution of clinical, genetic, and therapeutic factors to the first occurrence of time-dependent cardiac events (CEs) from age 1 to 41 years.Of the 391 patients, 118 (41 males, 77 females) patients (30%) experienced at least 1 CE (syncope, aborted cardiac arrest, or long-QT syndrome-related sudden death), and 24 (20%) suffered from LQT3-related aborted cardiac arrest/sudden death. The risk of a first CE was directly related to the degree of QTc prolongation. Cox regression analysis revealed that time-dependent β-blocker therapy was associated with an 83% reduction in CEs in females (P=0.015) but not in males (who had many fewer events), with a significant sex × β-blocker interaction (P=0.04). Each 10-ms increase in QTc duration up to 500 ms was associated with a 19% increase in CEs. Prior syncope doubled the risk for life-threatening events (P<0.02).Prolonged QTc and syncope predispose patients with LQT3 to life-threatening CEs. However, β-blocker therapy reduces this risk in females; efficacy in males could not be determined conclusively because of the low number of events.
Management of hormone-secreting pituitary adenomas
Authors: Gautam U. Mehta, Russell R. Lonser
Journal: Neuro-Oncology (2016)

Pituitary adenomas are one of the most common primary central nervous system tumors and have an estimated prevalence of 17%. Approximately half of pituitary adenomas secrete distinct pituitary hormones (most often prolactin, growth hormone, or adrenocorticotropic hormone). While these tumors are histologically benign, they have potent endocrine effects that lead to significant morbidity and shortened lifespan. Because of their pathophysiologic endocrine secretion and anatomic location near critical neural/vascular structures, hormone-secreting pituitary adenomas require defined management paradigms that can include relief of mass effect and biochemical remission. Management of hormone-secreting pituitary adenomas involves a multidisciplinary approach that can incorporate surgical, medical, and/or radiation therapies. Early and effective treatment of hormone-secreting pituitary adenomas can reduce morbidity and mortality. Consequently, understanding clinical features as well as therapeutic options in the context of the specific biological features of each type of hormone-secreting pituitary adenoma is critical for optimal management.