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https://www.readbyqxmd.com/read/28626519/discovery-of-potent-and-selective-tricyclic-inhibitors-of-bruton-s-tyrosine-kinase-with-improved-druglike-properties
#1
Xiaojing Wang, James Barbosa, Peter Blomgren, Meire C Bremer, Jacob Chen, James J Crawford, Wei Deng, Liming Dong, Charles Eigenbrot, Steve Gallion, Jonathon Hau, Huiyong Hu, Adam R Johnson, Arna Katewa, Jeffrey E Kropf, Seung H Lee, Lichuan Liu, Joseph W Lubach, Jen Macaluso, Pat Maciejewski, Scott A Mitchell, Daniel F Ortwine, Julie DiPaolo, Karin Reif, Heleen Scheerens, Aaron Schmitt, Harvey Wong, Jin-Ming Xiong, Jianjun Xu, Zhongdong Zhao, Fusheng Zhou, Kevin S Currie, Wendy B Young
In our continued effort to discover and develop best-in-class Bruton's tyrosine kinase (Btk) inhibitors for the treatment of B-cell lymphomas, rheumatoid arthritis, and systemic lupus erythematosus, we devised a series of novel tricyclic compounds that improved upon the druglike properties of our previous chemical matter. Compounds exemplified by G-744 are highly potent, selective for Btk, metabolically stable, well tolerated, and efficacious in an animal model of arthritis.
June 8, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28614800/robust-memory-responses-against-influenza-vaccination-in-pemphigus-patients-previously-treated-with-rituximab
#2
Alice Cho, Bridget Bradley, Robert Kauffman, Lalita Priyamvada, Yevgeniy Kovalenkov, Ron Feldman, Jens Wrammert
Rituximab is a therapeutic anti-CD20 monoclonal antibody widely used to treat B cell lymphoma and autoimmune diseases, such as rheumatic arthritis, systemic lupus erythematosus, and autoimmune blistering skin diseases (AIBD). While rituximab fully depletes peripheral blood B cells, it remains unclear whether some preexisting B cell memory to pathogens or vaccines may survive depletion, especially in lymphoid tissues, and if these memory B cells can undergo homeostatic expansion during recovery from depletion...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28610655/the-diagnosis-and-treatment-of-sj%C3%A3-gren-s-syndrome
#3
Ana-Luisa Stefanski, Christian Tomiak, Uwe Pleyer, Thomas Dietrich, Gerd Rüdiger Burmester, Thomas Dörner
BACKGROUND: Sjögren's syndrome is one of the more common inflammatory rheumatological diseases, with a prevalence of at least 0.4% in Germany. METHODS: This review is based on pertinent articles retrieved by a selective search in PubMed. Special attention is drawn to updated classification criteria and current treatment recommendations. RESULTS: Sjögren's syndrome has a wide variety of presentations, ranging from the local involvement of exocrine glands with keratoconjunctivitis sicca and xerostomia (the leading signs of the disease) to the systemic, extraglandular involvement of multiple organs...
May 26, 2017: Deutsches Ärzteblatt International
https://www.readbyqxmd.com/read/28571224/waldmann-s-disease-primary-intestinal-lymphangiectasia-with-atrial-septal-defect
#4
Shrikiran Aroor, Suneel Mundkur, Shravan Kanaparthi, Sandeep Kumar
Waldmann's disease or Primary Intestinal Lymphangiectasia (PIL) is a rare disorder of gastrointestinal tract characterized by dilated lymphatics and widened villi causing leakage of lymph into intestinal lumen. Loss of lymph leads to hypoalbuminemia, hyogammaglobulinemia and lymphopenia. Secondary lymphangiectasia occurs secondary to an elevated lymphatic pressure as in lymphoma, systemic lupus erythematosus, constrictive pericarditis, cardiac surgeries (Fontan's procedure), inflammatory bowel disease and malignancies...
April 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28508950/malignancy-as-a-comorbidity-in-rheumatic-diseases-a-retrospective-hospital-based-study
#5
Hai-Long Wang, Yong-Ming Zhou, Guang-Zhao Zhu, Zhu Yang, Bao-Jin Hua
Patients with Rheumatic diseases (RDs) are at an increased risk of malignancies compared with the general population. The aim of this study was to examine the relative frequency of several cancers in a single homogeneous cohort of patients with different RDs. Patients diagnosed with rheumatoid arthritis (RA), Ankylosing spondylitis (AS), Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM), or polymyositis were included. Out of 3982 adult residents admitted to the division of rheumatology, 61 malignancies were observed...
May 16, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28502938/successful-treatment-of-catastrophic-antiphospholipid-antibody-syndrome-associated-with-malt-lymphoma-by-autologous-hematopoietic-stem-cell-transplantation
#6
Satoko Oka, Kazuo Ono, Masaharu Nohgawa
A 37-year-old woman with extranodal marginal-zone lymphoma was admitted with a fever, hemiplegia, and severe dyspnea after chemotherapy. Catastrophic antiphospholipid antibody syndrome (CAPS) was suspected based on the histopathological confirmation of small-pulmonary vessel occlusion, evidence of the involvement of three organs, and elevated lupus anticoagulant assay results in a short time span. The patient responded to the initial treatment. One month later, the CAPS and lymphoma relapsed, and the patient underwent autologous hematopoietic stem cell transplantation...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28502334/ap-1-expression-and-its-clinical-relevance-in-immune-disorders-and-cancer
#7
REVIEW
Shivtia Trop-Steinberg, Yehudit Azar
The inflammatory response is known to have a significant role in certain autoimmune diseases and malignancies. We review current knowledge regarding the functions of activator protein 1 (AP-1) as an important modulator in several immune disorders and carcinomas. AP-1 is overexpressed in rheumatoid arthritis and in long-term allogeneic hematopoietic stem cell transplantation survivors; however, decreased expression of AP-1 has been observed in psoriasis, systematic lupus erythematosus and in patients who do not survive after hematopoietic stem cell transplantation...
May 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28428903/sle-and-non-hodgkin-s-lymphoma-a-case-series-and-review-of-the-literature
#8
Prajwal Boddu, Abdul S Mohammed, Chandrahasa Annem, Winston Sequeira
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder punctuated by varied multiorgan complications all along the course of its natural history. Lymphoma represents a relatively well-recognized malignant phenomenon associated with lupus. The cause and effect relationships of lymphoma in SLE have been subject to extensive scrutiny with several studies reporting on clinic-pathologic characteristics and risk factors predicting lymphoma development in SLE. However, the pathogenic role of immunosuppressives in SLE-related lymphoma still remains unclear, and indices to help guide diagnosis, prognostication, therapy, and posttreatment monitoring are yet to be established...
2017: Case Reports in Rheumatology
https://www.readbyqxmd.com/read/28424927/development-of-new-extra-glandular-manifestations-or-associated-auto-immune-diseases-after-establishing-the-diagnosis-of-primary-sj%C3%A3-gren-s-syndrome-a-long-term-study-of-the-antonius-nieuwegein-sj%C3%A3-gren-ans-cohort
#9
E J Ter Borg, J C Kelder
To investigate in a long-term study, the development of new extra-glandular manifestations (EGM) or associated auto-immune diseases (AID) from 1 year after establishing the diagnosis of primary Sjögren's syndrome (pSS). The primary goal was to examine the frequency and type of these manifestations and to find out which demographic, clinical and serological profile was most at risk. All outpatients diagnosed with primary Sjögren's syndrome were included in a retrospective study, with at least one check-up per year, from June 1991 until August 2015...
April 19, 2017: Rheumatology International
https://www.readbyqxmd.com/read/28365190/-kikuchi-fujimoto-disease-mimicking-malignant-lymphoma-in-adolescents
#10
A Escudier, S Courbage, V Meignin, S Abbou, S Sauvion, M Houlier, A Galerne, J Gaudelus, L de Pontual, M Simonin
Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis, is a rare cause of lymphadenopathy in children. This benign disease can mimic lymphoma and misleads doctors. It was first described in Asia, where it occurred especially in young women. Recent publications show that it can also affect teenagers and young adults in Caucasian populations. The pathophysiology remains unknown. Three hypotheses have been raised for this disease: the role of viruses (in particular HHV-8), genetic predisposition (two alleles in HLA class II genes were found more frequently in patients with Kikuchi disease), and an autoimmune cause because of the correlation with lupus erythematosus...
May 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/28357165/persistent-afebrile-abdominal-pain-an-unusual-case-of-segmental-colitis-in-an-immunocompromised-host
#11
Ilias P Papakonstantinou, Emmanuel A Andreadis
In this report we describe a case of a 66-year-old woman who presented with right upper quadrant abdominal pain and bloody diarrhea. A workup revealed immunodeficiency, an immunologic profile with low complement levels resembling systemic lupus erythematosus, and a circumferential colonic wall lesion located in the ascending colon. After endoscopy and biopsy, the mass lesion was attributed to "double hit" diffuse large B-cell lymphoma, categorized as high grade large B-cell non-Hodgkin lymphoma according to the most recent revised 2016 World Health Organisation classification and considered to be a rare and highly aggressive tumor...
February 16, 2017: Curēus
https://www.readbyqxmd.com/read/28346398/sirtuin-1-sirt1-overexpression-in-baf3-cells-contributes-to-cell-proliferation-promotion-apoptosis-resistance-and-pro-inflammatory-cytokine-production
#12
Qian Wang, Chao Yan, Miaomiao Xin, Li Han, Yunqing Zhang, Mingshu Sun
BACKGROUND B lymphocyte hyperactivity is a main characteristic of systemic lupus erythematosus (SLE), and B lymphocytes play a prominent pathogenic role in the development and progression of SLE. The aim of this study was to investigate the role of Sirtuin 1 (Sirt1) in B lymphocytes. MATERIAL AND METHODS Mouse B lymphocytes BaF3 was transfected with Sirt1 vector or shRNA against Sirt1. Then the transfected cells viability and apoptosis were respectively determined by MTT assay and flow cytometry. In addition, the mRNA levels of three pro-inflammatory cytokines and p53 were detected by RT-PCR...
March 27, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28293057/kikuchi-fujimoto-disease-a-rare-presentation-with-localized-iliac-lymphadenitis
#13
Shrihari Anil Anikhindi, Anil Arora, Shashi Dhawan, Naresh Bansal, Praveen Sharma, Vikas Singla, Ashish Kumar
Kikuchi-Fujimoto disease (KFD) is a benign, self-limiting disease characterized by histiocytic necrotising lymphadenitis. Though several viral agents or an autoimmune etiology has been proposed as causative, the exact cause remains unknown. It has a female predilection and most commonly seen among young Asian people. Patients usually present with a febrile illness and the presence of lymphadenopathy may provide a clue to diagnosis. The most common site of lymphadenopathy is cervical lymph nodes while intra-abdominal involvement is uncommon...
January 2017: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28274793/pkk-deficiency-in-b-cells-prevents-lupus-development-in-sle-lupus-mice
#14
D Oleksyn, J Zhao, A Vosoughi, J C Zhao, R Misra, A P Pentland, D Ryan, J Anolik, C Ritchlin, J Looney, A P Anandarajah, G Schwartz, L M Calvi, M Georger, C Mohan, I Sanz, L Chen
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies that can result in damage to multiple organs. It is well documented that B cells play a critical role in the development of the disease. We previously showed that protein kinase C associated kinase (PKK) is required for B1 cell development as well as for the survival of recirculating mature B cells and B-lymphoma cells. Here, we investigated the role of PKK in lupus development in a lupus mouse model...
May 2017: Immunology Letters
https://www.readbyqxmd.com/read/28263097/transcriptional-and-epigenetic-regulation-of-follicular-t-helper-cells-and-their-role-in-autoimmunity
#15
Hong Qiu, Haijing Wu, Vera Chan, Chak-Sing Lau, Qianjin Lu
T-follicular helper (Tfh) cells are a specialized subset of T cells that provide help to B cells and promote the formation of germinal centers (GCs). Tfh cells transmit important signals to B cells that drive class switch recombination, somatic hyper-mutation, the generation of high-affinity antibodies, immunological memory and their differentiation into plasma cells or memory B cells in the GCs. Tfh-cell differentiation is regulated by the coordinated functions of distinct cytokines, including interleukin (IL)-6, IL-21, IL-12, IL-23, IL-2, IL-7 and transforming growth factor-β (TGF-β), as well as transcription factors, including B-cell lymphoma 6 protein (Bcl-6), Signal transducers and activators of transcription (STAT)1, STAT3, STAT4, B-cell activating transcription factor (Batf), interferon regulatory factor 4 (IRF4), v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (C-Maf), T-cell-specific transcription factor 1 (TCF-1) and Achaete-scute homolog 2 (Acl2), which have been shown to form a complex transcriptional network...
March 2017: Autoimmunity
https://www.readbyqxmd.com/read/28195263/kikuchi-fujimoto-disease-a-clinicopathologic-update
#16
F Pepe, S Disma, C Teodoro, P Pepe, G Magro
Kikuchi-Fujmoto disease (KFD), also known as "histiocytic necrotizing lymphadenitis", is a rare lymphadenitis of unknown origin, but with an excellent prognosis. It is more common in Asia, but isolated cases are also reported in America, Africa and Europe. The disease can have an acute or subacute course, usually develops in 1 to 3 weeks, with spontaneous resolution in 1-4 months. The main clinical sign is cervical lymphadenopathy, especially in the posterior cervical triangle with bulky and painful lymph nodes, usually affecting only one side; rare cases of generalized lymphadenopathy can be seen...
September 2016: Pathologica
https://www.readbyqxmd.com/read/28175923/cutaneous-gamma-delta-t-cell-lymphoma-with-an-initially-indolent-course-mimicking-lupus-panniculitis
#17
Johannes Benecke, Cyrill Géraud, Jan P Nicolay
No abstract text is available yet for this article.
February 8, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28169015/janus-kinase-inhibitors-in-dermatology-a-systematic-review
#18
REVIEW
Rony Shreberk-Hassidim, Yuval Ramot, Abraham Zlotogorski
BACKGROUND: Janus kinase (JAK) inhibitors are emerging as a promising new treatment modality for many inflammatory conditions. OBJECTIVE: Our aim was to systematically review the available data on the use of JAK inhibitors in cutaneous diseases. METHODS: This is a systematic review of PubMed and ClinicalTrials.gov. RESULTS: One hundred thirty-four articles matched our search terms, of which 78 were original articles and 12 reports on adverse events...
April 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28152659/development-of-primary-central-nervous-system-lymphoma-in-a-systemic-lupus-erythematosus-patient-after-treatment-with-mycophenolate-mofetil-and-review-of-the-literature
#19
M A Balci, G E Pamuk, E Unlu, U Usta, O N Pamuk
Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma and four cases of PCNSL have previously been described in association with mycophenolate mofetil. We report the fifth case of PCNSL in a patient with lupus nephropathy while on mycophenolate mofetil treatment.
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28091805/correlation-between-systemic-lupus-erythematosus-and-malignancies-a-cross-sectional-population-based-study
#20
Shir Azrielant, Shmuel Tiosano, Abdulla Watad, Naim Mahroum, Aaron Whitby, Doron Comaneshter, Arnon D Cohen, Howard Amital
Autoimmune conditions reflect dysregulation of the immune system; this may be of clinical significance in the development of several malignancies. Previous studies show an association between systemic lupus erythematosus (SLE) and the development of malignancies; however, their investigations into the development of specific malignancies are inconsistent, and their external validity may be questionable. The main objective of this study is to investigate the association between the presence of SLE and various malignancies, in a large-scale population-based study...
April 2017: Immunologic Research
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