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Autoimmune blood disorders

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https://www.readbyqxmd.com/read/28809927/in-middle-aged-and-old-obese-patients-training-intervention-reduces-leptin-level-a-meta-analysis
#1
Ildikó Rostás, László Pótó, Péter Mátrai, Péter Hegyi, Judit Tenk, András Garami, Anita Illés, Margit Solymár, Erika Pétervári, Ákos Szűcs, Andrea Párniczky, Dániel Pécsi, Zoltán Rumbus, Csaba Zsiborás, Nóra Füredi, Márta Balaskó
BACKGROUND: Leptin is one of the major adipokines in obesity that indicates the severity of fat accumulation. It is also an important etiological factor of consequent cardiometabolic and autoimmune disorders. Aging has been demonstrated to aggravate obesity and to induce leptin resistance and hyperleptinemia. Hyperleptinemia, on the other hand, may promote the development of age-related abnormalities. While major weight loss has been demonstrated to ameliorate hyperleptinemia, obese people show a poor tendency to achieve lasting success in this field...
2017: PloS One
https://www.readbyqxmd.com/read/28803824/the-clinical-spectrum-of-hepatic-manifestations-in-chronic-lymphocytic-leukemia
#2
REVIEW
Natalia Kreiniz, Ofrat Beyar Katz, Aaron Polliack, Tamar Tadmor
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world, characterized by the presence of long-lived circulating leukemic cells in the peripheral blood that may infiltrate all organs, particularly those of the reticulo-endothelial system. Liver enlargement and elevation of liver enzymes related to specific involvement by the underlying disease are well-recognized features in these patients. In CLL, the differential diagnosis of liver disorders is broad and includes liver infiltration by leukemic cells, immunologic manifestations associated with CLL, primary and secondary hepatic malignancies, drug-induced hepatotoxicity, infections, and Richter transformation...
July 23, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28801357/the-autoimmune-risk-variant-ptpn22-c1858t-alters-b-cell-tolerance-at-discrete-checkpoints-and-differentially-shapes-the-naive-repertoire
#3
Genita Metzler, Xuezhi Dai, Christopher D Thouvenel, Socheath Khim, Tania Habib, Jane H Buckner, David J Rawlings
A common genetic variant in the gene encoding the protein tyrosine phosphatase nonreceptor type 22 (PTPN22 C1858T) has been linked to a wide range of autoimmune disorders. Although a B cell-intrinsic role in promoting disease has been reported, the mechanism(s) through which this variant functions to alter the preimmune B cell repertoire remains unknown. Using a series of polyclonal and transgenic self-reactive models harboring the analogous mutation in murine Ptpn22, we show evidence for enhanced BCR, B cell-activating factor receptor, and CD40 coreceptor programs, leading to broadly enhanced positive selection of B cells at two discrete checkpoints in the bone marrow and spleen...
August 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28791286/autoimmune-thrombotic-thrombocytopenic-purpura-two-rare-cases-associated-with-juvenile-idiopathic-arthritis-and-multiple-sclerosis
#4
Despoina Dimopoulou, Athina Dimosiari, Eudokia Mandala, Theodoros Dimitroulas, Alaxandros Garyfallos
Secondary thrombotic microangiopathies are associated with several underlying conditions, with most of them being resolved after the treatment of background disease. Thrombotic thrombocytopenic purpura (TTP) is a rare microangiopathy presenting with anemia, thrombocytopenia, and neurological deficits, occurring most often in various autoimmune diseases due to inhibition of ADAMTS13 by autoantibodies, as well as in pregnant women with or without an autoimmune substrate. In this article, we report two newly diagnosed TTP cases, who have not been published so far...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28783685/homodimerization-attenuates-the-anti-inflammatory-activity-of-interleukin-37
#5
Andrew M Ellisdon, Claudia A Nold-Petry, Laura D'Andrea, Steven X Cho, Jason C Lao, Ina Rudloff, Devi Ngo, Camden Y Lo, Tatiana P Soares da Costa, Matthew A Perugini, Paul J Conroy, James C Whisstock, Marcel F Nold
Dysregulation of the inflammatory response underlies numerous diseases. Although most interleukin-1 family cytokines are proinflammatory, human interleukin-37 (IL-37) is a powerful, broad-spectrum inhibitor of inflammation and immunity. We determined the crystal structure of IL-37 to establish the anti-inflammatory mechanism of this key cytokine in view of developing IL-37-based therapies. We found that two β-trefoil fold IL-37 molecules form a head-to-head dimer that is stable in solution. IL-37 variants mutated to convert the cytokine into an obligate monomer were up to 13-fold more effective than the dimer in suppressing proinflammatory events both in primary human blood cells and in vivo in murine endotoxic shock...
February 10, 2017: Science Immunology
https://www.readbyqxmd.com/read/28780512/repeated-administration-of-dapirolizumab-pegol-in-a-randomised-phase-i-study-is-well-tolerated-and-accompanied-by-improvements-in-several-composite-measures-of-systemic-lupus-erythematosus-disease-activity-and-changes-in-whole-blood-transcriptomic-profiles
#6
Chris Chamberlain, Peter J Colman, Ann M Ranger, Linda C Burkly, Geoffrey I Johnston, Christian Otoul, Christian Stach, Miren Zamacona, Thomas Dörner, Murray Urowitz, Falk Hiepe
OBJECTIVES: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease associated with diffuse immune cell dysfunction. CD40-CD40 ligand (CD40L) interaction activates B cells, antigen-presenting cells and platelets. CD40L blockade might provide an innovative treatment for systemic autoimmune disorders. We investigated the safety and clinical activity of dapirolizumab pegol, a polyethylene glycol conjugated anti-CD40L Fab' fragment, in patients with SLE. METHODS: This 32-week randomised, double-blind, multicentre study (NCT01764594) evaluated repeated intravenous administration of dapirolizumab pegol in patients with SLE who were positive for/had history of antidouble stranded DNA/antinuclear antibodies and were on stable doses of immunomodulatory therapies (if applicable)...
August 5, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28779866/neurological-complications-of-rheumatic-disease
#7
Svetlana Lvovich, Donald P Goldsmith
Rheumatic disease represents a broad spectrum of systemic conditions manifested by multisystem involvement and mediated by autoimmunity and inflammation. Their neurological complications may occur at any point in the disease process and are diagnostically challenging. For years central nervous system (CNS) was considered as a system uniquely protected from effects of the immune system because of the blood-brain barrier. Indeed, under physiological conditions immune access to CNS is tightly regulated. Over the past decade, new scientific discoveries highlighted pathways by which immune and neurological systems interact, including a variety of mechanisms controlling permeability of blood-brain barrier, and specific roles that CD4(+) and CD8(+) T-lymphocytes play in initiation of specific adaptive immune response to neural specific antigens...
February 2017: Seminars in Pediatric Neurology
https://www.readbyqxmd.com/read/28769929/autoimmune-regulator-deficiency-results-in-a-decrease-in-stat1-levels-in-human-monocytes
#8
Ofer Zimmerman, Lindsey B Rosen, Muthulekha Swamydas, Elise M N Ferre, Mukil Natarajan, Frank van de Veerdonk, Steven M Holland, Michail S Lionakis
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by biallelic autoimmune regulator (AIRE) mutations that manifests with chronic mucocutaneous candidiasis (CMC) and autoimmunity. Patients with STAT1 gain-of-function (GOF) mutations also develop CMC and autoimmunity; they exhibit increased STAT1 protein levels at baseline and STAT1 phosphorylation (pSTAT1) upon interferon (IFN)-γ stimulation relative to healthy controls. AIRE interacts functionally with a protein that directly regulates STAT1, namely protein inhibitor of activated STAT1, which inhibits STAT1 activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28766982/serum-met-5-enkephalin-levels-are-reduced-in-multiple-sclerosis-and-restored-by-low-dose-naltrexone
#9
Michael D Ludwig, Ian S Zagon, Patricia J McLaughlin
Low-dose naltrexone is a widely used off-label therapeutic prescribed for a variety of immune-related disorders. The mechanism underlying low-dose naltrexone's efficacy for fatigue, Crohn's disease, fibromyalgia, and multiple sclerosis is, in part, intermittent blockade of opioid receptors followed by upregulation of endogenous opioids. Short, intermittent blockade by naltrexone specifically blocks the opioid growth factor receptor resulting in biofeedback events that increase production of the endogenous opioid growth factor (OGF) (chemically termed [Met(5)]-enkephalin) facilitating interactions between opioid growth factor and opioid growth factor receptor that ultimately, result in inhibited cell proliferation...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28763062/pathogen-mediated-nmda-receptor-autoimmunity-and-cellular-barrier-dysfunction-in-schizophrenia
#10
G Kannan, K L Gressitt, S Yang, C R Stallings, E Katsafanas, L A Schweinfurth, C L G Savage, M B Adamos, K M Sweeney, A E Origoni, S Khushalani, S Bahn, F M Leweke, F B Dickerson, R H Yolken, M V Pletnikov, E G Severance
Autoantibodies that bind the N-methyl-D-aspartate receptor (NMDAR) may underlie glutamate receptor hypofunction and related cognitive impairment found in schizophrenia. Exposure to neurotropic pathogens can foster an autoimmune-prone environment and drive systemic inflammation leading to endothelial barrier defects. In mouse model cohorts, we demonstrate that infection with the protozoan parasite, Toxoplasma gondii, caused sustained elevations of IgG class antibodies to the NMDAR in conjunction with compromised blood-gut and blood-brain barriers...
August 1, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28744150/radiofrequency-ablation-using-barrx-%C3%A2-for-the-endoscopic-treatment-of-gastric-antral-vascular-ectasia-a-series-of-three-cases-and-a-review-of-the-literature-on-treatment-options
#11
Anish Patel, Sunil Patel, Prasanna C Wickremesinghe, Deepak Vadada
Gastric antral vascular ectasia (GAVE), also known as "watermelon stomach", is an uncommon condition, which can cause gastrointestinal bleeding due to rupture of blood vessels that line the stomach. The pathogenesis of GAVE remains unclear; however it is thought that hemodynamic changes, mechanical stress, and autoimmune factors all have a part to play. A range of conditions are also commonly associated with the syndrome, such as portal hypertensive gastropathy, liver cirrhosis, and autoimmune disorders. Less commonly, chronic renal failure, cardiac diseases, and bone marrow transplantation have coexisted with GAVE...
2017: Clinical and Experimental Gastroenterology
https://www.readbyqxmd.com/read/28742141/bruton-s-tyrosine-kinase-inhibitor-bms-986142-in-experimental-models-of-rheumatoid-arthritis-enhances-efficacy-of-agents-representing-clinical-standard-of-care
#12
Kathleen M Gillooly, Claudine Pulicicchio, Mark A Pattoli, Lihong Cheng, Stacey Skala, Elizabeth M Heimrich, Kim W McIntyre, Tracy L Taylor, Daniel W Kukral, Shailesh Dudhgaonkar, Jignesh Nagar, Dana Banas, Scott H Watterson, Joseph A Tino, Aberra Fura, James R Burke
Bruton's tyrosine kinase (BTK) regulates critical signal transduction pathways involved in the pathobiology of rheumatoid arthritis (RA) and other autoimmune disorders. BMS-986142 is a potent and highly selective reversible small molecule inhibitor of BTK currently being investigated in clinical trials for the treatment of both RA and primary Sjögren's syndrome. In the present report, we detail the in vitro and in vivo pharmacology of BMS-986142 and show this agent provides potent and selective inhibition of BTK (IC50 = 0...
2017: PloS One
https://www.readbyqxmd.com/read/28741259/adoptive-transfer-of-autoimmune-splenic-dendritic-cells-to-lupus-prone-mice-triggers-a-b-lymphocyte-humoral-response
#13
Daniela Sauma, Natalia Crisóstomo, Camila Fuentes, María Alejandra Gleisner, Yessia Hidalgo, María José Fuenzalida, Mario Rosemblatt, María Rosa Bono
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by increased autoantibody production that leads to multiple tissue injuries. Dendritic cells (DCs) are important orchestrators of immune responses and key components in fine-tuning the balance between tolerance and immunity. However, their role in autoimmune disorders such as SLE remains uncertain. We analyzed the contribution of DCs in triggering SLE by adoptively transferring splenic DCs from aged autoimmune [NZB×NZW]F1 (BWF1) mice to young healthy BWF1 mice...
July 25, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28733034/decreased-expression-of-mir-150-mir146a-and-mir424-in-type-1-diabetic-patients-association-with-ongoing-islet-autoimmunity
#14
Guofeng Wang, Yong Gu, Ning Xu, Mei Zhang, Tao Yang
BACKGROUND: Recent studies revealed altered miRNAs profiling in patients with autoimmune diseases, including type 1 diabetes (T1D). Here, we conducted an observational study and examined the expression levels of these five miRNAs (miR-150,miR-146a,miR-424,miR-181a and miR-142-3P) in peripheral blood mononuclear cells (PBMCs) from T1D patients. METHODS: PBMCs were obtained from T1D cohorts (n = 78), type 2 diabetes (T2D, n = 46) and healthy control subjects (n = 56)...
July 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28731851/the-frequency-of-occurrence-of-fish-shaped-red-blood-cells-in-different-haematologic-disorders
#15
Christoph Robier, Carolin Körber, Franz Quehenberger, Manfred Neubauer, Albert Wölfler
BACKGROUND: Red blood cells (RBC) resembling the silhouette of a fish are rarely observed in peripheral blood (PB) smears. In this study, we determined the frequency of occurrence of fish-shaped RBC in different haematologic diseases. METHODS: We examined PB smears of patients with iron deficiency anaemia (IDA) (n=23), β-thalassaemia minor (BTM) (n=30), sickle cell disease (SCD) (n=7), autoimmune haemolytic anaemia (AIHA) (n=13), microangiopathic haemolytic anaemia (MAHA) (n=11), hereditary sphaerocytosis (HS) (n=4), hereditary elliptocytosis (HE) (n=3), vitamin B12 and folate deficiency (n=15), anaemia in liver disease (LD) (n=17), myelodysplastic syndrome (MDS) (n=15), acute myeloid leukaemia (AML) (n=29), chronic myeloid leukaemia (CML) (n=18), primary myelofibrosis (PMF) (n=12), chronic myelo-monocytic leukaemia (CMML) (n=15) and 21 healthy controls by light microscopy for the occurrence of fish-shaped erythrocytes...
July 21, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28726667/clinical-and-genetic-peculiarities-of-vascular-manifestations-of-antiphospholipid-syndrome-case-report
#16
D Vasylyev, L Chernobay, O Vasylieva, M Oliinyk, M Vashuk
Pathogenetic mechanisms of the development of antiphospholipid syndrome (APS) are considered in the article, which is the basis for the development of clinical manifestations and laboratory markers of APS. The modern literature data are analyzed, according to which the presence of antiphospholipid antibodies is a hypercoagulable background, and the formation of thrombi occurs under the influence of other allowing procoagulation factors. The classification of the main types of hereditary thrombophilia is given, which is the primary disorder, against the background of which an autoimmune thrombosis APS develops...
June 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28717429/circulating-concentrations-of-interleukin-il-17-in-patients-with-multiple-sclerosis-evaluation-of-the-effects-of-gender-treatment-disease-patterns-and-il-23-receptor-gene-polymorphisms
#17
Seyed Ali Ghaffari, Maryam Nemati, Hossain Hajghani, Hossainali Ebrahimi, Abdolkarim Sheikhi, Abdollah Jafarzadeh
Background: Interleukin (IL)-17/IL-23 axis performs a prominent role in the pathogenesis of several autoimmune disorders. This study aimed to investigate the concentrations of IL-17 in patients with multiple sclerosis (MS) and its relationship with gender, medication, disease forms and single nucleotide polymorphisms (SNP) in IL-23R gene, including rs11209026 and rs1004819. Methods: The blood specimens were obtained from 135 healthy individuals and 135 MS patients. The patients exhibited relapsing-remitting (RRMS; n = 65), primary progressive (PPMS; n = 19), secondary progressive (SPMS; n = 35) or progressive relapsing (PRMS; n = 14) MS...
January 5, 2017: Iranian Journal of Neurology
https://www.readbyqxmd.com/read/28710878/6-mercaptopurine-modifies-cerebrospinal-fluid-t-cell-abnormalities-in-paediatric-opsoclonus-myoclonus-as-steroid-sparer
#18
M R Pranzatelli, E D Tate, T J Allison
The purpose of this study was to evaluate the capacity of 6-mercaptopurine (6-MP), a known immunosuppressant, to normalize cerebrospinal fluid (CSF) lymphocyte frequencies in opsoclonus-myoclonus syndrome (OMS) and function as a steroid sparer. CSF and blood lymphocytes were immunophenotyped in 11 children with OMS (without CSF B cell expansion) using a comprehensive panel of cell surface adhesion, activation and maturation markers by flow cytometry, and referenced to 18 paediatric controls. Drug metabolites, lymphocyte counts and liver function tests were used clinically to monitoring therapeutic range and toxicity...
July 15, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28702747/management-of-supine-hypertension-complicating-neurogenic-orthostatic-hypotension
#19
Jacquie Baker, Kurt Kimpinski
Neurogenic orthostatic hypotension (NOH) can be present in a number of disorders, including synucleinopathies, autoimmune disorders, and various genetic disorders. All are characterized by defective norepinephrine release from sympathetic terminals upon standing, resulting in impaired vasoconstriction. NOH is defined as a drop in systolic blood pressure ≥20 mmHg or diastolic blood pressure ≥10 mmHg, or both, within 3 minutes of standing or head up-tilt at a minimum of 60°. However, approximately 50% of patients have associated supine hypertension, which greatly complicates treatment...
August 2017: CNS Drugs
https://www.readbyqxmd.com/read/28701182/do-we-really-need-to-differentiate-mesenchymal-stem-cells-into-insulin-producing-cells-for-attenuation-of-the-autoimmune-responses-in-type-1-diabetes-immunoprophylactic-effects-of-precursors-to-insulin-producing-cells
#20
Anshu Sharma, Rajni Rani
BACKGROUND: Type 1 diabetes (T1D) is a multifactorial autoimmune disorder where pancreatic beta cells are lost before the clinical manifestations of the disease. Administration of mesenchymal stem cells (MSCs) or MSCs differentiated into insulin-producing cells (IPCs) have yielded limited success when used therapeutically. We have evaluated the immunoprophylactic potentials of precursors to insulin-producing cells (pIPCs) and IPCs in nonobese diabetic (NOD) mice to ask a basic question: do we need to differentiate MSCs into IPCs or will pIPCs suffice to attenuate autoimmune responses in T1D? METHODS: Bone marrow-derived MSCs from Balb/c mice were characterized following the International Society for Cellular Therapy (ISCT) guidelines...
July 12, 2017: Stem Cell Research & Therapy
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