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https://www.readbyqxmd.com/read/28634110/pharmacological-rescue-of-ductal-cftr-rescue-pancreatic-and-salivary-glands-acinar-cells-and-tissue-function-in-mouse-models-of-autoimmune-diseases
#1
Mei Zeng, Mitchell Szymczak, Malini Ahuja, Changyu Zheng, Hongen Yin, William Swaim, John A Chiorini, Robert J Bridges, Shmuel Muallem
BACKGROUND & AIMS: Sjögren's syndrome and autoimmune pancreatitis (AIP) are disorders with decreased function of salivary, lacrimal glands, and the exocrine pancreas. NOD/ShiLTJ mice and mice transduced with the cytokine BMP6 develop Sjögren's syndrome and chronic pancreatitis and MRL/Mp mice are models of AIP. CFTR is a ductal Cl(-) channel essential for ductal fluid and HCO3(-) secretion. We used these models to ask: is CFTR expression altered in these diseases, does correction of CFTR correct gland function, and most notably, does correcting ductal function correct acinar function...
June 17, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28633442/continuous-glucose-monitoring-in-female-nod-mice-reveals-daily-rhythms-and-a-negative-correlation-with-body-temperature
#2
Ron Korstanje, Jennifer L Ryan, Holly S Savage, Bonnie L Lyons, Kevin G Kane, Stacey J Sukoff Rizzo
Previous studies with continuous glucose monitoring in mice have been limited to several days or weeks, with the mouse's physical attachment to the equipment impacting behavior and measurements. In the current study we measured blood glucose and body temperature at 10-second intervals for 12 weeks in a cohort of NOD/ShiLtJ female mice using wireless telemetry. This allowed us, for the first time, to obtain a high-resolution profile of the circadian rhythm of these two parameters and the onset of hyperglycemic development in real time...
June 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#3
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28617827/nog-hil-4-tg-a-new-humanized-mouse-model-for-producing-tumor-antigen-specific-igg-antibody-by-peptide-vaccination
#4
Yoshie Kametani, Ikumi Katano, Asuka Miyamoto, Yusuke Kikuchi, Ryoji Ito, Yukari Muguruma, Banri Tsuda, Sonoko Habu, Yutaka Tokuda, Kiyoshi Ando, Mamoru Ito
Immunodeficient mice transplanted with human peripheral blood mononuclear cells (PBMCs) are promising tools to evaluate human immune responses to vaccines. However, these mice usually develop severe graft-versus-host disease (GVHD), which makes estimation of antigen-specific IgG production after antigen immunization difficult. To evaluate antigen-specific IgG responses in PBMC-transplanted immunodeficient mice, we developed a novel NOD/Shi-scid-IL2rγnull (NOG) mouse strain that systemically expresses the human IL-4 gene (NOG-hIL-4-Tg)...
2017: PloS One
https://www.readbyqxmd.com/read/28611473/apc-targeted-proinsulin-expression-inactivates-insulin-specific-memory-cd8-t-cells-in-nod-mice
#5
Peta Ls Reeves, Rajeev Rudraraju, Xiao Liu, F Susan Wong, Emma E Hamilton-Williams, Raymond J Steptoe
Type 1 diabetes (T1D) results from T-cell mediated autoimmune destruction of pancreatic β cells. Effector T-cell responses emerge early in disease development and expand as disease progresses. Following β cell destruction, a long-lived T-cell memory is generated that represents a barrier to islet transplantation and other cellular insulin-replacement therapies. Development of effective immunotherapies that control or ablate β cell destructive effector and memory T cell responses has the potential to prevent disease progression and recurrence...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28594903/the-role-of-bone-marrow-mesenchymal-stromal-cell-derivatives-in-skin-wound-healing-in-diabetic-mice
#6
Tomas de Mayo, Paulette Conget, Silvia Becerra-Bayona, Claudia L Sossa, Virgilio Galvis, Martha L Arango-Rodríguez
Mesenchymal stromal cells (MSCs) have shown to be a promising tool in cell therapies to treat different conditions. Several pre-clinical and clinical studies have proved that the transplantation of MSCs improves wound healing. Here, we compare the beneficial effects of mouse bone marrow-derived allogeneic MSCs (allo-mBM-MSCs) and their acelullar derivatives (allo-acd-mMSCs) on skin wound healing in Non-Obese Diabetic (NOD) mice. One dose of allo-mBM-MSCs (1×106 cells) or one dose of allo-acd-mMSCs (1X) were intradermally injected around wounds in 8-10 week old female NOD mice...
2017: PloS One
https://www.readbyqxmd.com/read/28592649/oas1b-dependent-immune-transcriptional-profiles-of-west-nile-virus-infection-in-the-collaborative-cross
#7
Richard Green, Courtney Wilkins, Sunil Thomas, Aimee Sekine, Duncan M Hendrick, Kathleen Voss, Renee C Ireton, Michael Mooney, Jennifer T Go, Gabrielle Choonoo, Sophia Jeng, Fernando Pardo-Manuel de Villena, Martin T Ferris, Shannon McWeeney, Michael Gale
The oligoadenylate-synthetase (Oas) gene locus provides innate immune resistance to virus infection. In mouse models, variation in the Oas1b gene influences host susceptibility to flavivirus infection. However, the impact of Oas variation on overall innate immune programming and global gene expression among tissues and in different genetic backgrounds has not been defined. We examined how Oas1b acts in spleen and brain tissue to limit West Nile virus (WNV) susceptibility and disease across a range of genetic backgrounds...
June 7, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28592385/nucleotide-binding-oligomerization-domain-containing-protein-2-nod2-modulates-t1dm-susceptibility-by-gut-microbiota
#8
Yang-Yang Li, James A Pearson, Chen Chao, Jian Peng, Xiaojun Zhang, Zhiguang Zhou, Yu Liu, F Susan Wong, Li Wen
Nucleotide-binding oligomerization domain-containing protein 2 (Nod2) is an innate immune receptor. To investigate the role of Nod2 in susceptibility to the autoimmune disease, type 1 diabetes mellitus (T1DM), we generated Nod2(-/-) non-obese diabetic (NOD) mice. The Nod2(-/-)NOD mice had different composition of the gut microbiota compared to Nod2(+/+)NOD mice and were significantly protected from diabetes, but only when housed separately from Nod2(+/+)NOD mice. This suggested that T1DM susceptibility in Nod2(-/-)NOD mice is dependent on the alteration of gut microbiota, which modulated the frequency and function of IgA-secreting B-cells and IL-10 promoting T-regulatory cells...
June 4, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28580341/targeting-innate-immunity-to-downmodulate-adaptive-immunity-and-reverse-type-1-diabetes
#9
REVIEW
Arata Itoh, William M Ridgway
Type 1 diabetes (T1D) is characterized by specific destruction of pancreatic insulin-producing beta cells accompanied by evidence of beta-cell-directed autoimmunity such as autoreactive T cells and islet autoantibodies (IAAs). Currently, T1D cannot be prevented or reversed in humans. T1D is easy to prevent in the nonobese diabetic (NOD) spontaneous mouse model but reversing new-onset T1D in mice is more difficult. Since the discovery of the T-cell receptor in the 1980s and the subsequent identification of autoreactive T cells directed toward beta-cell antigens (eg, insulin, glutamic acid decarboxylase), the dream of antigen-specific immunotherapy has dominated the field with its promise of specificity and limited side effects...
2017: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/28578255/development-and-validation-of-an-ultra-performance-liquid-chromatography-tandem-mass-spectrometry-method-for-quantification-of-sr1001-an-inverse-agonist-of-retinoid-related-orphan-receptors-and-its-application-to-pharmacokinetic-studies-in-streptozotocin-induced
#10
Cuipei Lin, Hanqing Wang, Hua Sun, Chengju Xiao, Yunxia Xue, Jun Liu, Ting Fu, Yifei Wang, Dong Dong, Zhijie Li
Retinoic acid receptor-related orphan receptors (RORs) play critical roles in the onset and progression of type I diabetes, an autoimmune disease characterized by the destruction of pancreatic β-cells. SR1001, an ROR inverse agonist, has been proven to be an effective diabetes treatment in the non-obese diabetic (NOD) mouse model. However, optimization of this treatment is challenging because knowledge of SR1001 pharmacokinetic (PK) behaviors in type I diabetic animals is limited. The aim of our study was to develop and validate a specific and sensitive ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to measure the concentrations of SR1001 in plasma and biological samples...
May 24, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28550681/antibiotic-associated-manipulation-of-the-gut-microbiota-and-phenotypic-restoration-in-nod-mice
#11
James R Fahey, Bonnie L Lyons, Haiyan L Olekszak, Anthony J Mourino, Jeremy J Ratiu, Jeremy J Racine, Harold D Chapman, David V Serreze, Dina L Baker, N Ken Hendrix
Segmented filamentous bacterium (SFB) a gram-positive, anaerobic, and intestinal commensal organism directly influencesthe development of Th17 helper cells in the small intestine of mice. In NOD mice, SFB colonization interferes with the developmentof type 1 diabetes (T1D), a T-cell-mediated autoimmune disease, suggesting that SFB may influence Th17 cells to inhibit Th1populations associated with the anti-β-cell immune response. This effect is a serious concern for investigators who use NOD micefor diabetes research because the expected incidence of disease decreases markedly when they are colonized by SFB...
May 26, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28550041/central-nervous-system-involvement-in-acute-lymphoblastic-leukemia-is-mediated-by-vascular-endothelial-growth-factor
#12
Vera Münch, Luca Trentin, Julia Herzig, Salih Demir, Felix Seyfried, Johann M Kraus, Hans A Kestler, Rolf Köhler, Thomas F E Barth, Geertruy Te Kronnie, Klaus-Michael Debatin, Lüder H Meyer
In acute lymphoblastic leukemia (ALL), central nervous system (CNS) involvement is a major clinical concern. Despite non-detectable CNS leukemia in many cases, prophylactic CNS-directed conventional intrathecal chemotherapy is required for relapse free survival indicating subclinical CNS manifestation in most patients. However, CNS-directed therapy is associated with long-term sequelae including neurocognitive deficits and secondary neoplasms. Therefore, molecular mechanisms and pathways mediating leukemia cell entry into the CNS need to be understood in order to identify targets for prophylactic and therapeutic interventions and develop alternative CNS-directed treatment strategies...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28539651/an-orthologous-non-mhc-locus-in-rats-and-mice-is-linked-to-cd4-and-cd8-t-cell-proportion
#13
D Franckaert, R Collin, J Dooley, R H Wallis, P Poussier, A Liston, E E Hillhouse, S Lesage
CD4(+) and CD8(+) T cells have a central role in the immune system due to their ability to protect against infection and cancer development without targeting self. Consequently, changes in CD4(+) and CD8(+) T-cell homeostasis can be indicative of an array of serious illnesses, ranging from viral infections to autoimmune diseases. In addition to environmental influences, there is evidence for a genetic component regulating the proportion of CD4(+) and CD8(+) T cells in lymphoid organs. Indeed, identifying the genetic determinants defining the frequency of the T-cell subsets is critical as it may reveal a targetable genetic pathway to modulate CD4(+) and CD8(+) T-cell numbers, which could be of clinical relevance for multiple disease settings...
May 25, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28539439/contribution-of-human-lung-parenchyma-and-leukocyte-influx-to-oxidative-stress-and-immune-mediated-pathology-following-nipah-infection
#14
Olivier Escaffre, Tais B Saito, Terry L Juelich, Tetsuro Ikegami, Jennifer K Smith, David D Perez, Colm Atkins, Corri B Levine, Matthew B Huante, Rebecca J Nusbaum, Janice J Endsley, Alexander N Freiberg, Barry Rockx
Nipah virus (NiV) is a zoonotic emerging paramyxovirus that can cause a fatal respiratory illness or encephalitis in humans. Despite many efforts, the molecular mechanisms of NiV-induced acute lung injury (ALI) remain unclear. We previously showed that NiV replicates to high titers in human lung grafts in NOD scid gamma mice, resulting in a robust inflammatory response. Interestingly, these mice can undergo human immune system reconstitution by the Bone marrow, Liver, and Thymus (BLT) reconstitution method, in addition to lung tissue engraftment, giving altogether a realistic model to study human respiratory viral infections...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28536677/ccpa-affects-infectivity-of-staphylococcus-aureus-in-a-hyperglycemic-environment
#15
Markus Bischoff, Bodo Wonnenberg, Nadine Nippe, Naja J Nyffenegger-Jann, Meike Voss, Christoph Beisswenger, Cord Sunderkötter, Virginie Molle, Quoc Thai Dinh, Frank Lammert, Robert Bals, Mathias Herrmann, Greg A Somerville, Thomas Tschernig, Rosmarie Gaupp
Many bacteria regulate the expression of virulence factors via carbon catabolite responsive elements. In Gram-positive bacteria, the predominant mediator of carbon catabolite repression is the catabolite control protein A (CcpA). Hyperglycemia is a widespread disorder that predisposes individuals to an array of symptoms and an increased risk of infections. In hyperglycemic individuals, the bacterium Staphylococcus aureus causes serious, life-threatening infections. The importance of CcpA in regulating carbon catabolite repression in S...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28533295/comparative-pathogenesis-of-autoimmune-diabetes-in-humans-nod-mice-and-canines-has-a-valuable-animal-model-of-type-1-diabetes-been-overlooked
#16
Allison L O'Kell, Clive Wasserfall, Brian Catchpole, Lucy J Davison, Rebecka S Hess, Jake A Kushner, Mark A Atkinson
Despite decades of research in humans and mouse models of disease, substantial gaps remain in our understanding of pathogenic mechanisms underlying the development of type 1 diabetes. Furthermore, translation of therapies from preclinical efforts capable of delaying or halting β-cell destruction has been limited. Hence, a pressing need exists to identify alternative animal models that reflect human disease. Canine insulin deficiency diabetes is, in some cases, considered to follow autoimmune pathogenesis, similar to NOD mice and humans, characterized by hyperglycemia requiring lifelong exogenous insulin therapy...
June 2017: Diabetes
https://www.readbyqxmd.com/read/28526333/systemic-manifestations-of-primary-sj%C3%A3-gren-s-syndrome-in-the-nod-b10sn-h2-b-j-mouse-model
#17
Jeremy Kiripolsky, Long Shen, Yichen Liang, Alisa Li, Lakshmanan Suresh, Yun Lian, Quan-Zhen Li, Daniel P Gaile, Jill M Kramer
Animal models that recapitulate human disease are crucial for the study of Sjögren's Syndrome (SS). While several SS mouse models exist, there are few primary SS (pSS) models that mimic systemic disease manifestations seen in humans. Similar to pSS patients, NOD.B10Sn-H2(b)/J (NOD.B10) mice develop exocrine gland disease and anti-nuclear autoantibodies. However, the disease kinetics and spectrum of extra-glandular disease remain poorly characterized in this model. Our objective was to characterize local and systemic SS manifestations in depth in NOD...
May 17, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28511686/intrathymic-injection-of-hematopoietic-progenitor-cells-establishes-functional-t-cell-development-in-a-mouse-model-of-severe-combined-immunodeficiency
#18
Andrea Z Tuckett, Raymond H Thornton, Richard J O'Reilly, Marcel R M van den Brink, Johannes L Zakrzewski
BACKGROUND: Even though hematopoietic stem cell transplantation can be curative in patients with severe combined immunodeficiency, there is a need for additional strategies boosting T cell immunity in individuals suffering from genetic disorders of lymphoid development. Here we show that image-guided intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγ(null) mice is feasible and facilitates the generation of functional T cells conferring protective immunity...
May 16, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28507865/reconstitution-of-human-keloids-in-mouse-skin
#19
Ataru Sunaga, Hideaki Kamochi, Shunji Sarukawa, Hirokazu Uda, Yasushi Sugawara, Rintaro Asahi, Daekwan Chi, Shiho Nakagawa, Koji Kanayama, Kotaro Yoshimura
BACKGROUND: Keloids are a dermal fibroproliferative scar of unknown etiology. There is no good animal model for the study of keloids, which hinders the development and assessment of treatments for keloids. METHODS: Human keratinocytes and dermal fibroblasts were isolated from 3 human skin tissues: normal skin, white scars, and keloids. A mixed-cell slurry containing keratinocytes and dermal fibroblasts was poured into a double chamber implanted on the back of NOD/Shi-scid/IL-2Rγnull mice...
April 2017: Plastic and Reconstructive Surgery. Global Open
https://www.readbyqxmd.com/read/28507809/t-cell-therapy-targeting-a-public-neoantigen-in-microsatellite-instable-colon-cancer-reduces-in-vivo-tumor-growth
#20
Else M Inderberg, Sébastien Wälchli, Marit R Myhre, Sissel Trachsel, Hilde Almåsbak, Gunnar Kvalheim, Gustav Gaudernack
T-cell receptor (TCR) transfer is an attractive strategy to increase the number of cancer-specific T cells in adoptive cell therapy. However, recent clinical and pre-clinical findings indicate that careful consideration of the target antigen is required to limit the risk of off-target toxicity. Directing T cells against mutated proteins such as frequently occurring frameshift mutations may thus be a safer alternative to tumor-associated self-antigens. Furthermore, such frameshift mutations result in novel polypeptides allowing selection of TCRs from the non-tolerant T-cell repertoire circumventing the problem of low affinity TCRs due to central tolerance...
2017: Oncoimmunology
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