scholarly journals Rapamycin improves TIE2-mutated venous malformation in murine model and human subjects

2015 ◽  
Vol 125 (9) ◽  
pp. 3491-3504 ◽  
Author(s):  
Elisa Boscolo ◽  
Nisha Limaye ◽  
Lan Huang ◽  
Kyu-Tae Kang ◽  
Julie Soblet ◽  
...  
Keyword(s):  
Murine Model ◽  
Human Subjects ◽  
Venous Malformation

Abstract 77: Distinct Profiles of Transient Receptor Potential Canonical (TRPC) Channel Expression in Biventricular Failure

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Kevin J Morine ◽  
Vikram Paruchuri ◽  
Xiaoying Qiao ◽  
Duc T Pham ◽  
Gordon S Huggins ◽  
...  
Keyword(s):  
Heart Failure ◽  
Murine Model ◽  
Transient Receptor Potential ◽  
Human Subjects ◽  
Receptor Potential ◽  
Tissue Samples ◽  
Transient Receptor Potential Canonical ◽  
Biventricular Failure ◽  
Transient Receptor ◽  
End Stage

Heart failure is a major cause of morbidity and mortality. The transient receptor potential canonical (TRPC) family of channels mediate pathologic cardiac remodeling. In particular, TRPC6 participates in a self-propagating circuit that amplifies cardiac hypertrophy and fibrosis. The objective of this study was to explore biventricular expression of TRPCs in advanced heart failure. Methods: Viable left (LV) and right (RV) ventricular free wall tissue was obtained from human subjects with end-stage heart failure (n=12) referred for transplantation or biventricular assist devices. Control LV and RV tissue was obtained from the National Disease Research Interchange (n=3/group). To explore TRPC expression in a murine model, adult male C57BL/6 mice underwent thoracic aortic constriction (TAC) for 10 weeks (n=6/group). Biventricular tissue was analyzed by real-time polymerase chain reaction. Results: Compared to normal LV and RV, levels of TRPC 1, 3, 4 and 6 were increased in failing LV and RV samples, respectively. Levels of TRPC1 and TRPC6 were greater in failing RV than failing LV samples. TRPC 5 and 7 expression were not consistently detected in normal or failing tissue samples. Compared to sham LV, levels of TPRC 1, 4 and 6 increased in the LV after TAC. Compared to sham RV, levels of TRPC 3, 4, and 6 increased in the RV after TAC. Levels of TRPC3 were greater in the RV than LV after TAC. Conclusions: Our results identify distinct profiles of TRPC expression in the RV versus LV in both human tissue and in a murine model of advanced biventricular failure. Levels of select TRPCs are higher in the failing RV compared to LV, suggesting a potentially important role for TRPCs in RV remodeling.

Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

2019 ◽  
Vol 133 (22) ◽  
pp. 2283-2299
Author(s):  
Apabrita Ayan Das ◽  
Devasmita Chakravarty ◽  
Debmalya Bhunia ◽  
Surajit Ghosh ◽  
Prakash C. Mandal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Chronic Inflammation ◽  
Ex Vivo ◽  
Human Subjects ◽  
Critical Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Tnf Α ◽  
Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

Intradermal challenge with interleukin-8 causes tissue oedema and neutrophil accumulation in atopic and non-atopic human subjects

1996 ◽  
Vol 26 (12) ◽  
pp. 1371-1379 ◽  
Author(s):  
J. Douglass ◽  
D. Dhami ◽  
M. Bulpitt ◽  
I. J. Lindley ◽  
J. Shute ◽  
...  
Keyword(s):  
Human Subjects ◽  
Interleukin 8 ◽  
Neutrophil Accumulation ◽  
Tissue Oedema

Anti-OX40ligand treatment as a novel therapeutic strategy in a murine model of colitis

2001 ◽  
Vol 120 (5) ◽  
pp. A685-A685
Author(s):  
B SINGH ◽  
V MALMSTROM ◽  
F POWRIE
Keyword(s):  
Murine Model ◽  
Therapeutic Strategy ◽  
Novel Therapeutic

404: Immune Mediated Survival Advantage and Primary Tumor Control of Cryoablation Compared to Nephrectomy in a Murine Model of Advanced Renal Cancer

2006 ◽  
Vol 175 (4S) ◽  
pp. 132-132 ◽  
Author(s):  
Sean P. Hedican ◽  
Eric R. Wilkinson ◽  
Thomas F. Warner ◽  
Fred T. Lee ◽  
Stephen Y. Nakada
Keyword(s):  
Renal Cancer ◽  
Murine Model ◽  
Primary Tumor ◽  
Survival Advantage ◽  
Tumor Control ◽  
Advanced Renal Cancer ◽  
Immune Mediated

Research Recommendations for Applying Vitamin A-Labelled Isotope Dilution Techniques to Improve Human Vitamin A Nutrition

2014 ◽  
Vol 84 (Supplement 1) ◽  
pp. 52-59 ◽  
Author(s):  
Sherry A. Tanumihardjo ◽  
Anura V. Kurpad ◽  
Janet R. Hunt
Keyword(s):  
Public Health ◽  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Human Subjects ◽  
The Body ◽  
Pool Size ◽  
Serum Retinol ◽  
Vitamin A Status ◽  
Status Assessment ◽  
Total Body

The current use of serum retinol concentrations as a measurement of subclinical vitamin A deficiency is unsatisfactory for many reasons. The best technique available for vitamin A status assessment in humans is the measurement of total body pool size. Pool size is measured by the administration of retinol labelled with stable isotopes of carbon or hydrogen that are safe for human subjects, with subsequent measurement of the dilution of the labelled retinol within the body pool. However, the isotope techniques are time-consuming, technically challenging, and relatively expensive. There is also a need to assess different types of tracers and doses, and to establish clear guidelines for the use and interpretation of this method in different populations. Field-friendly improvements are desirable to encourage the application of this technique in developing countries where the need is greatest for monitoring the risk of vitamin A deficiency, the effectiveness of public health interventions, and the potential of hypervitaminosis due to combined supplement and fortification programs. These techniques should be applied to validate other less technical methods of assessing vitamin A deficiency. Another area of public health relevance for this technique is to understand the bioconversion of β-carotene to vitamin A, and its relation to existing vitamin A status, for future dietary diversification programs.

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